OVERVIEW
Lymphoma is a unique type of lymphoma, one of the most common malignant tumors in young people presenting as painless masses in the neck, supraclavicular and armpits, accompanied by fever, night sweats, and lethargy, etc. The etiology of the disease is unknown, and it may be related to viral infections, genetic factors, and other immune disorders Mainly used in the integrated treatment of chemotherapy, radiotherapy, targeted therapy, and immunotherapy
Definition
Hodgkin’s lymphoma (HL), also known as Hodgkin’s disease, is a hematologic malignancy that originates in the lymph nodes and mainly affects the lymph nodes, spleen, liver, and bone marrow.
The disease initially occurs in a group of lymph nodes, with the cervical lymph nodes and supraclavicular lymph nodes being the most common, and then spreads to other lymph nodes, and in the advanced stage, it may invade blood vessels, and involve the spleen, liver, bone marrow, and gastrointestinal tract.
Incidence
The incidence of Hodgkin’s lymphoma accounts for 5% to 10% of lymphomas, and is more common in males than females.
Hodgkin’s lymphoma accounts for approximately 4.8% of malignant tumors in childhood and 15% to 20% of childhood lymphomas.
GLOBOCAN 2020 data show that in 2020, there were 83,087 new cases of Hodgkin’s lymphoma globally, including 48,981 cases in men and 34,106 cases in women.
In 2020, there were 6829 new cases of Hodgkin’s lymphoma in China, including 4506 cases in males and 2323 cases in females.
The age of onset of Hodgkin’s lymphoma in China is early, and the median age of onset is around 30 years old.
Disease types
Hodgkin’s lymphoma is divided into classic lymphoma and nodular lymphocyte-dominant type, the latter accounting for about 10% of Hodgkin’s lymphoma.
Classic Hodgkin’s lymphoma is further subdivided based on histology:
Lymphocyte-rich type: histologic features include the presence of a small number of characteristic Ri-Schiff cells (R-S cells) and a large number of B cells.
Nodular sclerotic type: histology is characterized by dense fibrous tissue encompassing the tissue nodules of Hodgkin’s lymphoma.
Mixed-cell type: histologic features include the presence of a certain number of R-S cells, which is the most common type in China.
Lymphocyte ablation type: histologic features are the presence of a large number of R-S cells, lymphocytes are significantly reduced, and there may be diffuse fibrosis and necrotic foci.
Etiology
Pathogenic factors
The etiology of Hodgkin’s lymphoma is unknown and may be related to viral infections, genetic factors and other immune diseases.
Viral infections
EBV infection may be associated with the development of Hodgkin’s lymphoma.
People with human immunodeficiency virus (HIV) infection have a somewhat higher incidence of Hodgkin’s lymphoma than the general population.
Genetic factors
People with a family history of Hodgkin’s lymphoma have a higher risk of developing the disease than others.
Immunosuppression or defects
Patients who have had immunosuppressive drugs applied after transplantation.
People with congenital immunodeficiencies.
People with autoimmune diseases such as systemic lupus erythematosus and dry syndrome.
Predisposing factors
In addition to genetic factors, viral infections and other causative factors, some studies have shown that the incidence of the disease is relatively higher in people with better economic conditions or higher education. Frequent exposure to some environmental chemical exposures may also be associated with the development of Hodgkin’s lymphoma.
Symptoms
Main Symptoms
Enlarged lymph nodes: manifested by gradual enlargement of lymph nodes without pain. The most common sites are the neck and upper clavicle, and the lumps can be felt by touching with hands.
Fever: cyclic fever without cause, body temperature gradually rises to 38-40℃ within a few days, and after a few days, the temperature gradually drops to normal, which occurs in a repeated cycle, and the body temperature changes cyclically.
Wasting: rapid weight loss in a short period of time, can lose more than 10% of body weight in 6 months.
Itchy skin: some people have generalized itchy skin, mostly young women.
Night sweats: sweating after going to sleep and stopping after waking up, usually soaking the underwear at night.
Other symptoms
As the disease progresses, enlarged lymph nodes may compress neighboring organs and produce corresponding symptoms.
If it occurs in the chest, it may cause coughing, chest tightness and shortness of breath.
If it occurs in the liver, yellowing of the skin and sclera may occur.
If it invades the bone tissue, it will cause bone pain.
Metastatic manifestations
The most common way of metastasis of Hodgkin’s lymphoma is gradual invasion of nearby lymph nodes or extra-nodal tissues, and blood metastasis can also occur in the late stage to spread to the whole body.
Lymph node metastasis: there may be multiple lymph node enlargement all over the body.
Liver metastasis: manifested by loss of appetite, sometimes accompanied by nausea, vomiting, etc.; vague pain in the right upper abdomen, persistent or intermittent pain in the liver area, sometimes aggravated by changes in body position; fatigue, emaciation, unexplained fever and edema; yellowing of the skin and sclera, ascites, itching of the skin.
Peritoneal metastasis: metastasis to the peritoneum appearing as ascites.
Intracranial metastasis: metastasis to the intracranium may present headache, optic disc edema and other clinical manifestations of increased intracranial pressure.
Consultation
Department of Medicine
Department of Hematology
If there are unexplained fever, night sweats, weight loss, fatigue, etc., which do not improve after symptomatic treatment, or painless and gradually increasing neck nodular protuberance or swelling, one should consult a doctor promptly.
Lymphoma Diagnosis and Treatment Center
If you are diagnosed with Hodgkin’s lymphoma, you can also go to a lymphoma center or medical oncology department of a specialized oncology hospital.
Preparation
Consultation Information: Registration, Preparation of Documents, Frequently Asked Questions
Tips for Medical Consultation
It is recommended to wear clothes that are easy to put on and take off before the consultation so that the doctor can examine the patient easily.
If the patient is young, parents should help to calm down and cooperate with the examination.
Preparation Checklist
Symptom list
Pay particular attention to the time of onset of symptoms, special manifestations, etc.
Is there any nodule-like protrusion or lump in the neck?
Is there a persistent fever of unknown origin?
Is there any night sweating that requires changing clothes and bedding?
Any recent localized or generalized itching of the skin?
Any unexplained weight loss?
Medical History Checklist
Has anyone in the family had lymphoma or other malignant tumors?
Are there any infections such as EBV, Human Immunodeficiency Virus (HIV), etc.?
Are there any immune system disorders such as rheumatoid arthritis, dry syndrome, etc.?
Has there been an organ transplant?
Any drug or food allergies?
Checklist
Test results in the last six months, which can be brought to the doctor’s office
Specialized tests: blood smear, bone marrow imaging, lymph node biopsy
Laboratory tests: blood tests, biochemical tests
Imaging tests: ultrasonography, CT scan, magnetic resonance imaging (MRI), PET-CT
Diagnosis
Diagnostic basis
When the doctor suspects Hodgkin’s lymphoma, he or she needs to ask for medical history and perform physical examination such as neck palpation, laboratory tests such as routine blood and blood biochemistry, pathological tests such as lymph node biopsy, bone marrow aspiration, lymphocyte differentiation antigen test, and imaging tests such as ultrasound, X-ray, CT, and PET-CT.
Medical history
History of viral infections, such as HIV, EBV infections, etc.
History of autoimmune diseases, such as systemic lupus erythematosus, dry syndrome, etc.
History of congenital immunodeficiency.
History of immunosuppressant use.
Family history of Hodgkin’s lymphoma.
Clinical manifestations
Symptoms
Initially, unexplained fever, chest pain, cough or shortness of breath may occur in some patients.
As the disease progresses, night sweats, weight loss, itching and fatigue may occur.
Signs and symptoms
Early stage Hodgkin’s lymphoma may present with unexplained swelling of superficial lymph nodes, which are commonly found in the neck and supraclavicular region.
Liver and spleen enlargement may also be seen in middle and advanced Hodgkin’s lymphoma.
Laboratory Tests
Routine blood test
Routine blood test can help doctors know whether the number of white blood cells, lymphocytes, eosinophils, erythrocyte sedimentation rate and monocytes is normal or not, and whether there is anemia, which can help doctors make preliminary judgment on the patient’s condition.
Blood biochemistry test
Lactate dehydrogenase helps to infer the patient’s prognosis.
Serum alkaline phosphatase or blood calcium can help to know whether the lesion has invaded the bones.
Bone marrow biopsy
A bone marrow smear that reveals R-S cells indicates the presence of bone marrow invasion.
Elderly patients and immunodeficient patients are more likely to have bone marrow invasion.
Histologic examination
Pathology
The diagnosis of Hodgkin’s lymphoma is based on the pathologic examination of the diseased tissue.
Patients with progressive, painless lymph node enlargement require lymph node prints, pathologic sections, or smears of lymph node aspirates.
After the pathological diagnosis, it is also necessary to determine the scope of the lesion according to the systemic symptoms, physical examination, laboratory examination and imaging examination, etc., to clarify the clinical stage and formulate the treatment plan.
Immunohistochemistry
Immunohistochemistry can be used to detect the expression levels of various proteins in oncological diseases to make a diagnosis and determine the prognosis.
The detection of CD15, CD20, CD30 and EMA not only diagnose Hodgkin’s lymphoma, but also determine the pathologic subtype and assist in the development of treatment plans.
Imaging
Ultrasound: It can detect enlarged lymph nodes that are difficult to find during physical examination.
X-ray examination: Chest X-ray examination can find out whether there are lesions in the chest cavity, such as whether there are morphological changes in the mediastinum and hilar, whether there are lesions in the lungs, and whether there is pleural fluid.
CT: Chest CT examination can not only find out whether there are lesions in the lungs, but also determine whether there are enlarged lymph nodes in the mediastinum and hilar of the lungs of the patient, and their sizes and exact locations, etc., whether there is any compression of the trachea, blood vessels, and neighboring lung tissues, and also find out whether there is any pleural effusion, pericardial effusion, and chest wall mass.
PET-CT: PET-CT can localize the lymphoma lesions, which can help to accurately stage the patient’s disease and comprehensively evaluate the treatment effect, and is an important imaging examination method.
Clinical staging
The staging of Hodgkin’s lymphoma generally adopts the Ann Arbor staging system modified by Cotswold, which is mainly divided into two parts: stage and symptom type.
Stage
Hodgkin’s lymphoma can be categorized into stages I, II, III and IV according to the extent of lesions.
Criteria for staging
Ⅰ The lesion is confined to one lymph node area or one extra-lymph node organ or site.
Ⅰ
The lesion is confined to one lymph node area or one extra-lymph node organ or site.
Ⅱ The lesion is confined to two or more lymph node areas on the same side of the diaphragm, or spreads directly to adjacent extra-lymph node organs or sites.
II
Lesions limited to two or more lymph node areas on the same side of the diaphragm, or directly spreading to adjacent extra-lymph node organs or sites
III Involvement of lymph node regions on both sides of the diaphragm, or involvement of an additional extra-lymph node organ or site
III
Involvement of lymph node areas on both sides of the diaphragm, or involvement of an additional extra-lymph node organ or site
IV Diffuse or disseminated involvement of one or more extra-lymph node organs, such as liver and bone marrow
IV
Diffuse or disseminated involvement of one or more extra-lymphoid organs, e.g., liver and bone marrow
Symptom type
On the basis of staging, two types, A and B, are also classified according to the presence or absence of associated symptoms.
Criteria for differentiation
A is not accompanied by clinical symptoms.
A
Not accompanied by clinical symptoms.
B Presence of at least one of the following symptoms: ① Weight loss of 10% or more without intentional dieting or strenuous exercise within 6 months ② Persistent or recurrent fever with body temperature exceeding 38°C ③ Persistent night sweats
B
Presence of at least one of the following symptoms: ① weight loss of 10% or more without intentional dieting or strenuous exercise within 6 months ② persistent or recurrent fever with body temperature exceeding 38℃ ③ persistent night sweats.
Differential Diagnosis
Infectious mononucleosis
Similarities: both can have fever, lymph node swelling and other symptoms, the pathogen can be EBV, and both are common in adolescents.
Differences: Infectious mononucleosis lymph node biopsy often shows unclear lymph node structure, immunoblast hyperplasia, and R-S cells are usually not seen microscopically. Therefore, differential diagnosis can be made with the help of pathologic examination.
Burkitt’s lymphoma
Similarities: Both may present with symptoms such as enlarged lymph nodes, both are caused by EBV infection, and both are common in children and adolescent males.
Differences: Burkitt’s lymphoma usually presents with swelling of the neck and jaw, and may also involve the intestines and the periorbital area. Immunohistochemistry and molecular testing can help. Tumor cells in Burkitt’s lymphoma are immunohistochemically positive for CD10, positive for BCL-6, negative for BCL-2, and have a cell proliferation index (Ki-67) of ≥80%. Therefore, it can be differentiated with the help of symptoms and immunohistochemistry.
Mesenchymal large cell lymphoma
Similarities: Both may present with symptoms such as enlarged lymph nodes, skin nodules, fever, night sweats and weight loss.
Differences: skin invasion is common in mesenchymal large cell lymphoma, and the main clinical manifestation is red nodules or plaque-like changes in the skin; in addition, mesenchymal large cell lymphoma cells express B-cell-associated antigens CD20 and CD79α, and generally seldom express CD10 and CD138; therefore, it can be differentiated with the help of symptoms and immunohistochemistry.
Treatment
Principles of treatment
Hodgkin’s lymphoma is sensitive to chemotherapy, and the treatment adopts a combination of chemotherapy as the mainstay and radiotherapy as a supplement, while targeted therapy, immunotherapy and autologous hematopoietic stem cell transplantation can be considered in some patients.
At present, the treatment plan for Hodgkin’s lymphoma is mainly based on histologic typing and clinical staging, and combined with prognostic factors. Patients who have the condition can choose to select the appropriate treatment plan under the guidance of PET-CT.
For drug treatment, please strictly follow the doctor’s instructions and do not self-medicate.
Treatment of classic Hodgkin’s lymphoma
Treatment of classic Hodgkin’s lymphoma is stratified according to the stage and the presence of poor prognostic factors.
The main chemotherapy regimens include:
ABVD chemotherapy regimen: doxorubicin, bleomycin, vincristine, and dacarbazine.
Enhanced dose BEACOPP regimen: bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone.
Stage I-II
These patients were treated with a combination of chemotherapy combined with radiotherapy, and were divided into a good prognosis group and a poor prognosis group according to the presence or absence of adverse prognostic factors.
Good prognosis group
Two to four cycles of ABVD regimen chemotherapy combined with radiotherapy is the standard treatment.
Based on the mid-term PET-CT efficacy evaluation, those who were PET-CT negative after 2 cycles of chemotherapy with ABVD regimen were continued to be given 1 to 2 cycles of ABVD regimen followed by 20 Gy of radiotherapy, while those who were PET-CT positive were treated with 2 cycles of chemotherapy with enhanced dose BEACOPP regimen and 30 Gy of radiotherapy.
Poor prognosis group
4 cycles of ABVD regimen chemotherapy combined with 30 Gy radiotherapy was the standard treatment.
If intermediate PET-CT evaluation was performed after 2 cycles of chemotherapy with ABVD regimen, those with negative PET-CT were continued with 2 more cycles of chemotherapy with ABVD regimen followed by radiotherapy (30Gy).
And those with positive PET-CT were changed to enhanced dose BEACOPP regimen chemotherapy for 2 cycles and radiotherapy (30Gy).
For younger patients less than 60 years old, an intensified regimen is available, with 2 cycles of enhanced-dose BEACOPP regimen chemotherapy given followed by 2 cycles of ABVD regimen and combined radiotherapy (30 Gy).
Stage III-IV
The principle of treatment is usually chemotherapy, and local radiotherapy is limited to those with residual lesions of more than 2.5 cm after chemotherapy.
Younger patients less than 60 years of age may be given 6 cycles of chemotherapy with the ABVD regimen or 4 to 6 cycles of the booster dose BEACOPP regimen, with or without local radiotherapy.
Interim PET-CT examination after chemotherapy with the ABVD regimen is recommended after 2 cycles of chemotherapy; if the result is negative, chemotherapy with the AVD (doxorubicin + vincristine + dacarbazide) regimen can be used for the subsequent 4 cycles.
If the test result is positive, 4 cycles of chemotherapy with ABVD or booster dose BEACOPP regimen is feasible.
If the test result is negative, chemotherapy with the BEACOPP regimen is continued for 2 cycles (4 cycles in total), and if the test result is positive, chemotherapy with the BEACOPP regimen is performed for another 4 cycles (6 cycles in total).
If the efficacy of the first-line treatment does not achieve complete remission (CR), autologous hematopoietic stem cell transplantation is suitable.
Treatment of Nodular Lymphocyte-Predominant Hodgkin’s Lymphoma
No clinical prognostic factors
Stage IA patients without clinical prognostic factors can be treated with radiotherapy alone (30Gy), and the treatment of the remaining stages is based on the principles of treatment of classical Hodgkin’s lymphoma.
Regimen of plus Tolterizumab
Because of the positive CD20 expression of this type of tumor cells, chemotherapy ± rituximab ± radiotherapy can be used for treatment. Chemotherapy regimens can be chosen from ABVD, CHOP (cyclophosphamide + doxorubicin + vincristine + prednisone), and CVP (cyclophosphamide + vincristine + prednisone) regimens.
Re-biopsy is recommended for suspected relapse to rule out transformation to aggressive lymphoma, and rituximab monotherapy can be applied to those with limited lesions at relapse, and rituximab combined with second-line salvage regimen can be chosen for those with extensive lesions.
Treatment of relapsed/refractory Hodgkin’s lymphoma
Preferred second-line salvage regimen chemotherapy followed by high-dose chemotherapy combined with autologous hematopoietic stem cell transplantation.
Salvage regimen
DHAP (dexamethasone, high-dose cytarabine, cisplatin), ICE (isocyclophosphamide, carboplatin, etoposide), and IGEV (isocyclophosphamide, gemcitabine, and vincristine) regimens are available.
Targeted therapy and immunotherapy
The main relevant drugs currently approved by the National Drug Administration (NMPA) for lymphoma treatment include:
Sindilizumab, Karelizumab and Tirilizumab: for the treatment of relapsed or refractory classical Hodgkin’s lymphoma after second-line systemic chemotherapy.
Vibutuximab: for the treatment of relapsed or refractory Hodgkin’s lymphoma.
Hematopoietic Stem Cell Transplantation
Young patients who have relapsed after autologous hematopoietic stem cell transplantation and are still sensitive to chemotherapy may be considered for allogeneic hematopoietic stem cell transplantation.
Chinese medicine treatment
Some Chinese medicine treatments or drugs can improve the condition in clinic, and it is recommended to go to regular medical institutions under the guidance of physicians.
TCM treatment can be used as an adjuvant treatment for Hodgkin’s lymphoma, which can help reduce the adverse effects of radiotherapy.
Chinese medicine treatment can help regulate the immune function and physical condition of patients, improve the quality of life of Hodgkin’s lymphoma, and have a certain effect on improving the long-term survival rate of Hodgkin’s lymphoma patients.
Special reminder: secret prescriptions, biased prescriptions, folk remedies and other methods of treatment have no scientific basis, and their effectiveness and safety are difficult to be guaranteed, so they are not recommended to be used.
Prognosis
Prognostic factors
Prognostic factors refer to the factors that affect the overall survival and quality of life of patients. A patient’s prognosis is related to the grade and stage of the tumor, treatment, and individual constitution.
The most commonly used prognostic evaluation system for advanced Hodgkin’s lymphoma is the International Prognostic Score, which consists of 7 adverse factors, with each additional adverse factor increasing the risk of recurrence by 7% to 8%.
Albumin <40 g/L.
Hemoglobin <105 g/L.
Male.
Age ≥45 years; and
Stage IV lesions.
Leukocytosis, leukocyte count ≥15×109/L.
Lymphopenia with <8% of leukocytes and/or lymphocyte count <0.6×109/L.
In addition, patients with negative PET-CT after 2 to 3 cycles of chemotherapy had a significantly better prognosis than those with positive PET-CT.
Survival
The overall prognosis of Hodgkin’s lymphoma is good, and the 5-year survival rate is generally around 90%.
The 5-year survival rate of Chinese patients with early-stage classical Hodgkin’s lymphoma is 96.7%, and the 5-year survival rate of patients with advanced stage is 86.0%.
[Special Reminder
The overall survival time of cancer patients can be roughly predicted by the 5-year or 10-year survival rate, which refers to the proportion of patients whose tumors survive for 5 years or 10 years or more after various comprehensive treatments.The probability of recurrence after 5 or 10 years is very low, and it can generally be regarded as a clinical cure.
Statistics such as the 5- or 10-year survival rate are for clinical research only and do not represent an individual’s specific survival period.
Daily
Treatment-related care
Leukopenia: When white blood cells are reduced, infections will occur more easily. During chemotherapy, pay attention to warmth and rest, avoid catching cold, and reduce close contact with people to reduce the risk of infection.
Anorexia, nausea and vomiting: Eat small meals and eat easily digestible, light food. If necessary, consult your doctor if you need to take anti-emetic drugs.
Fever: For fever below 38℃, no antipyretic drugs can be used, drink plenty of warm water and pay attention to rest; if the body temperature exceeds 38℃ and there is obvious headache or general malaise, you should go to the hospital in time.
Generalized fatigue: This kind of fatigue is often related to anemia, which requires sufficient rest and nutrition, and adequate intake of calories and proteins can help relieve the discomfort. If necessary, ask your doctor if you need to take medication to correct your anemia.
Hair loss: Hair loss may occur during radiotherapy, but it will grow back after the treatment is over, so don’t worry too much.
Life management
Mindfulness and Emotional Adjustment
A good mood and mindset cannot be replaced by drugs.
After diagnosis, the patient may develop a sense of fear and may be afraid of pain, abandonment and death. Family members should pay attention to listen to the patient’s heart, improve the patient’s psychological tolerance and relieve anxiety symptoms.
Encourage the patient’s family to give spiritual support and psychological comfort, so that the patient can face the surgery and other treatments positively with a good mindset.
During the period between treatments and after treatment, family members are advised to encourage the patient to do work and household chores that are within his/her ability, and to actively integrate into social roles.
Living
The living environment should be kept clean, with sufficient ventilation, sufficient sunlight and suitable greenhouse. Disinfect the room regularly to avoid infection.
Maintain good hygiene and cleanliness, and wear a good mask when going out.
Avoid excessive activity and trauma for those who are prone to bleeding.
Dietary regulation
Balanced dietary structure, diversified food types and rich nutrition.
Avoid pickled, fried and deep-fried food.
Eat more vitamin-rich vegetables and fruits, such as tomatoes, celery, kiwi and apples.
Eat more protein-rich foods, such as eggs, milk, lean meat and fish.
Rest and exercise
Pay attention to rest, avoid staying up late or straining, and ensure sufficient sleep and rest to reduce physical exertion and promote recovery.
After the condition improves, you can start with low intensity exercise such as walking and gradually resume normal activities.
Follow-up examination
The main purpose of follow-up is to detect metastatic recurrence or its signs at an early stage so that timely intervention can be made to improve survival time and quality of life.
Time for follow-up