Overview of malignant tumors of the immune system
A malignant tumor of the immune system originating in the lymph nodes or lymphoid tissues. In the early stages, it is characterized by painless masses with fever, night sweats, and weight loss. The cause of the disease is not known, but viral infections, immune deficiencies, heredity, and environmental factors all play a role in the disease. Treatment is mainly pharmacological, with combination of radiotherapy and stem cell transplantation.
Definition
Lymphoma (lymphoma) originates in lymph nodes or lymphoid tissues, and most of its occurrence is related to the malignant transformation of a certain type of immune cell produced by the proliferation and differentiation of lymphocytes in the course of immune response, and it is a malignant tumor of the immune system [1].
Most types of lymphomas are staged with reference to the 2014 Lugano staging criteria (which is a modified version of the Ann Arbor-Cotswolds staging) and can be divided into stages I to IV. There is no clear definition of early stage, and stages I and II are often defined as early, while stages III and IV are advanced. If lymphoma is detected at an early stage, the therapeutic effect and prognosis will be much better than the late stage.
The term “malignant lymphoma” may be used in clinical practice or in daily life. In fact, all lymphomas are malignant tumors and there are no benign ones, only that different types of lymphomas have different degrees of malignancy.
For example, Hodgkin’s lymphoma is less malignant than non-Hodgkin’s lymphoma, and has a relatively better cure rate and prognosis, but both are malignant tumors.
Classification
According to histopathological changes, lymphomas can be classified into Hodgkin’s lymphoma (HL) and non-Hodgkin’s lymphoma (NHL). Generally, the former has a relatively better prognosis, while the prognosis of the latter varies depending on the type [1,3].
Hodgkin’s lymphoma
Once known as Hodgkin’s disease.
There are two main types: nodular lymphocyte-dominant type and classic type.
The nodular lymphocyte-dominant type accounts for approximately 10% of HL.
Classic HL accounts for about 90% of HL and is subdivided into nodular sclerosing, lymphocyte-rich, lymphocyte-absent, and mixed-cell types [3].
The prognosis of Hodgkin’s lymphoma is not entirely consistent across different subtypes, but is relatively favorable overall.
Non-Hodgkin’s lymphoma
Non-Hodgkin’s lymphomas (NHL) are a diverse group of malignant tumors with different sites of onset and histologic features, which are prone to spread to other lymph node regions or other tissues and organs.
Non-Hodgkin’s lymphomas that progress more slowly and have a longer natural course are also known as “inert lymphomas”.
The World Health Organization (WHO) has identified different types of NHL as separate diseases based on their pathologic characteristics, and the following are some of the common types [3].
Diffuse large B-cell lymphoma (DLBCL)
It is the most common type of NHL, accounting for about 40% of NHL in Chinese adults.
Follicular lymphoma (FL)
Follicular lymphoma (FL) is a common “inert lymphoma” of mature B-lymphocyte origin, accounting for 2.5%-6.6% of NHL in China, with a median age of onset of 49 years.
Marginal zone lymphoma (MZL)
MZL is a relatively slow-progressing “inert lymphoma”.
It includes three subtypes: mucosa-associated lymphoid tissue (MALT) lymphoma, intranodal marginal zone lymphoma, and splenic marginal zone lymphoma, with MALT being the most common.
Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL)
Domestic incidence is low, accounting for about 6% to 7% of NHL. The median age of onset is 65 years, and the male-to-female ratio is (1.5 to 2):1.
Murine cell lymphoma (MCL)
Derived from B-cells and characterized by both inert and aggressive lymphoma.
It accounts for about 5% of all NHLs in China.
It is more common in older men, with a male-to-female ratio of (2-3):1, and a median age of onset of about 65 years.
Burkitt’s lymphoma/leukemia (BL)
It is a highly aggressive NHL that can be categorized into 3 variants: endemic, disseminated, and immunodeficiency-associated.
It accounts for 1% to 3% of all NHL and 40% of childhood NHL.
Lymphoblastic lymphoma (LBL)
Accounts for approximately 2% to 4% of adult NHL and is more common in children or adolescents. The male-to-female incidence ratio is more than 2.5:1.
Peripheral T-cell lymphoma, non-specific (PTCL-NOS)
Originates from post-thymic mature T cells.
It is aggressive and has a poor prognosis.
Commonly seen in middle-aged and elderly patients, with a median age of onset of 55 years and no significant gender differences.
Mycosis fungoides (MF) and Sézary syndrome (SS)
MF, also known as mycosis fungoides, and SS are the most common cutaneous T-cell lymphomas.
Nasal-type NK/T-cell lymphoma (ENKTL)
It is an EBV-associated lymphoma, and more than 90% of patients are positive for EBV.
ENKTL is more common in Asia and South America, and very rare in Europe and the United States.
It is most common in males and has a younger age of onset.
Morbidity
Since there are no incidence data for early stage of lymphoma, the overall epidemiologic data of lymphoma can be referred to.
Lymphoma is one of the common malignant tumors in China, the vast majority of which are non-Hodgkin’s lymphomas. According to the latest statistics of China in 2020 [3]:
In 2016, the overall incidence rate of lymphoma in China was 6.5/100,000, which is equivalent to 6-7 people per 100,000 people developing lymphoma [1-2].
In 2020, there were 99,663 new cases of lymphoma nationwide, including 6,829 cases of Hodgkin’s lymphoma, accounting for only 6.85%, and 92,834 cases of non-Hodgkin’s lymphoma, accounting for 93.15%. Compared with the data of 89,900 new cases of lymphoma in the country in 2016 [2], the incidence rate is significantly higher.
In 2020, a total of 57,158 people died of lymphoma nationwide, of which 2,807 cases of Hodgkin’s lymphoma deaths accounted for 4.91%, and 54,351 cases of non-Hodgkin’s lymphoma deaths accounted for 95.09%.
The incidence and mortality rates of male non-Hodgkin’s lymphoma ranked 10th among all malignant tumors; the incidence and mortality rates of female non-Hodgkin’s lymphoma did not enter the top 10 of all malignant tumors.
China’s Hodgkin’s lymphoma has an early age of onset, with a median age of onset around 30 years old, and there are more men than women.
The highest incidence rate in adults in China is diffuse large B-cell lymphoma, with a median age of onset of 50 to 70 years, slightly higher in men than in women.
Burkitt’s lymphoma and lymphoblastic lymphoma are common in children and adolescents.
Causes
The cause of lymphoma is not yet fully understood, and may be related to certain bacterial and viral infections, immunodeficiency or suppression, genetic factors and environmental factors.
Causes of disease
The early stage of lymphoma is a necessary stage of lymphoma, and its etiology is consistent with that of lymphoma. There is no clear cause of lymphoma.
High risk factors
It is generally believed that infectious, immunologic, physicochemical, and genetic factors play an inescapable role in the development of lymphoma, and these factors are also known as high-risk factors for the development of lymphoma [1,3-4].
Viruses and bacteria
EBV (Epstein-Barr Virus).
EBV infection is closely associated with the development of malignant lymphoma.
In cases of Hodgkin’s lymphoma, the EBV detection rate can be as high as 75%.
In nasal-type NK/T-cell lymphomas, the EBV test positivity rate can be 90% to 100%.
Latent EBV infection is present in almost 100% of endemic Burkitt’s lymphomas in Africa.
Human T-cell leukemia virus-1 (HTLV-1)
HTLV-1 is thought to be the cause of adult T-cell leukemia/lymphoma.
Helicobacter pylori (Hp)
Hp infection is associated with the development of gastric mucosa-associated lymphoid tissue lymphoma.
Immunodeficiency or suppression
Lymphomas are malignant tumors of the immune system, and immunocompromise of the body is an important cause and pathogenetic condition of lymphoma.
HIV-infected patients, patients with systemic lupus erythematosus, patients with rheumatoid arthritis, and certain patients who need long-term treatment with immunosuppressive drugs (such as patients who have received organ transplantation), etc., have a significantly higher incidence of lymphoma than normal people.
Occupational exposure and environmental factors
Long-term exposure to solvents, leather, dyes, pesticides and herbicides increases the risk of lymphoma.
Woodworking industry workers will be exposed to wood dust and benzene for a long time, and the incidence rate of Hodgkin’s lymphoma is relatively higher than that of the general population.
The incidence of plasma cell myeloma is also increased in people who are chronically exposed to radiation, such as hospital radiology and nuclear power plant workers.
Genetic factors
Lymphoma is sometimes concentrated in a particular family, suggesting that its development is genetically related.
First-degree relatives of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma have a two- to seven-fold increased risk of developing lymphoma.
The prevalence of lymphoma in close relatives of patients with plasma cell myeloma is more than 3.7 times higher than in the general population.
Note: First-degree relatives are parents, children, and siblings.
Symptoms
Early symptoms of lymphoma are mostly characterized by painless lymph node enlargement.
Hodgkin’s Lymphoma
Enlarged lymph nodes
In China, the first symptom of 90% of Hodgkin’s lymphoma patients is enlarged lymph nodes [3].
Enlargement of cervical lymph nodes and supraclavicular lymph nodes are the most common, followed by axillary lymph node enlargement.
The enlarged lymph nodes can be mobile or adherent to each other and fused into a mass with a cartilage-like sensation on palpation.
If there is simultaneous invasion of the lymph node regions above and below the diaphragm, or invasion of organs outside the lymph nodes, such as the spleen, it is no longer in the early stages.
B Symptoms
According to the presence or absence of the following three systemic symptoms, patients can be categorized into two groups, A and B. Those who have none of the three symptoms belong to group A, while those who have at least one of them belong to group B. Therefore, the following symptoms are also referred to as B symptoms [1,3,5].
Unexplained fever over 38°C for more than 3 consecutive days, excluding infection. This may also be the first symptom in some patients.
Heavy sweating at night, which may even soak through clothing.
Weight loss of more than 10% in the six months prior to consultation.
Other common systemic symptoms
Lymph node pain after drinking alcohol is a characteristic symptom of Hodgkin’s lymphoma, but it does not occur in every patient.
There may be localized and generalized itching of the skin, most often in young women.
Herpes zoster occurs in a few patients [1,5-6].
Non-Hodgkin’s lymphoma
Lymph node enlargement
Painless persistent enlargement of lymph nodes or painless localized masses are common clinical manifestations in the early stages of lymphoma, and NHL is no exception [1,3].
In contrast to Hodgkin’s lymphoma, non-Hodgkin’s lymphoma also has the following characteristics:
Systemic: it can occur in any part of the body, jumping. Among them, lymph nodes, tonsils, spleen and bone marrow are the most likely sites to be involved.
Versatility: different tissues and organs, with different scope and degree of compression or invasion, cause different symptoms.
Systemic symptoms
In addition to the inert subtype, non-Hodgkin’s lymphoma generally develops rapidly, so systemic symptoms may also be present in the early stages [1].
Compression and invasion of organs by non-Hodgkin’s lymphoma is more common than that of Hodgkin’s lymphoma, and high fever or manifestations of invasion of organs and systems often occur.
Pharyngeal lymphatic ring lesions may be characterized by dysphagia, nasal congestion, rhinorrhea and enlarged submandibular lymph nodes.
The chest is most involved in the hilum and mediastinum, and half of them have lung invasion or pleural effusion, which may lead to cough, chest tightness, shortness of breath, pulmonary atelectasis and superior vena cava compression syndrome.
Involvement of the gastrointestinal tract is most common in the ileum, followed by the stomach. Clinical manifestations include abdominal pain, diarrhea, and abdominal masses, and the diagnosis is often confirmed by surgery for intestinal obstruction or massive bleeding.
Enlarged retroperitoneal lymph nodes may compress the ureter and cause hydronephrosis. Renal damage mainly includes nephromegaly, hypertension, renal insufficiency and nephrotic syndrome [6].
Seek medical attention
Prompt medical attention is recommended for symptoms such as unexplained fever and enlarged lymph nodes.
Department of Medicine
General surgery
If a lump is found in the neck or armpit, the general surgery department is the first place to be consulted.
Internal Medicine
Consult the appropriate internal medicine department according to the symptoms, such as respiratory medicine for coughing, gastroenterology for abdominal pain and diarrhea, and then refer to a specialist after confirming the diagnosis.
If you have a fever of unknown origin, you may need to consult the Fever Clinic first.
Oncology
If early stage lymphoma is suspected or diagnosed in other departments, you may also consult the Department of Oncology, Department of Lymphoma or Department of Hematology.
Preparation for medical treatment
Preparing for the consultation: registration, preparation of documents, and frequently asked questions
Tips for Consultation
Patients can organize their symptoms and questions before visiting the doctor. It is inevitable that questions will be missed due to the emotional stress of visiting the doctor.
Preparation Checklist
Symptom list
Pay particular attention to the time of onset of symptoms, special manifestations, etc.
Is there any unexplained fever, loss of weight, night sweats, itchy skin?
Is there any localized pain in the body after drinking alcohol?
Any unexplained abdominal pain, diarrhea, abdominal discomfort, etc.?
List of medical history
Is there any diagnosed malignant tumor in the family?
Have you ever been tested for EBV or H. pylori? If so, what were the results and was there any treatment?
What is your occupation? Any chronic exposure to wood dust, solvents, leather, dyes, pesticides and herbicides?
Any other chronic illnesses?
Checklist
Test results from the last six months, which you can bring with you to the doctor’s office
Specialty tests: tumor markers, pathology results.
Laboratory tests: blood routine, urine routine, stool routine, biochemical tests.
Imaging examination: CT examination, magnetic resonance (MRI), PET-CT.
Medication list
Medication use in the last 3 months, including tumor-related or non-related drugs
Immunosuppressive drugs: e.g. hormones, immunosuppressants, chemotherapeutic drugs, etc.
Symptomatic drugs: e.g. antipyretics, analgesics, etc.
Diagnosis
Pathologic diagnosis is the gold standard for lymphoma diagnosis [1].
Based on the histopathological examination results, the diagnosis of lymphoma and classification and typing diagnosis are made. After that, the lymphoma is then staged according to the AnnArbor clinical staging scheme based on the distribution range of the lymphoma.
Diagnosis is based on
Medical History
The patient may have a history of the following, but not all patients will develop lymphoma if they have a relevant medical history.
Family history of malignancy, especially lymphoma.
History of viral bacterial infections, such as EBV and Helicobacter pylori.
History of occupational or environmental exposure to hazardous substances, such as organic solvents, radiation, etc.
History of immune-related diseases, such as AIDS, autoimmune disease, long-term use of immunosuppressants, organ transplantation, etc.
Clinical manifestations
Enlarged lymph nodes in the neck, supraclavicular, axillary or other parts of the body.
Unexplained persistent fever, weight loss, night sweats, itchy skin.
Localized pain in the body after drinking alcohol.
Unexplained abdominal pain, diarrhea, and abdominal discomfort.
Laboratory Tests
Blood tests
Most patients with Hodgkin’s lymphoma in the early stage do not have anemia, and a small number of patients have mild to moderate anemia. White blood cells and platelets are usually normal [5].
Non-Hodgkin’s lymphoma white blood cell counts are mostly normal and lymphocytes may be increased.
Helicobacter pylori (Hp) testing
Lymphoma that initially occurs in the stomach (gastric lymphoma) requires Hp testing [2].
Imaging
Imaging tests that are indispensable for the diagnosis of lymphoma include ultrasound, CT, MRI and PET-CT.
Ultrasound examination of the superficial lymph nodes can identify missed palpations on physical examination.
Chest CT can identify mediastinal and hilar lymph node enlargement, and understand pleural effusion and lung lesions, etc. CT is also the preferred method of abdominal examination.
Positron emission computed tomography CT (PET-CT) can show lymphoma lesions and sites. PET-CT has been used as an important indicator for evaluating the efficacy of lymphoma [6].
Other imaging tests that may be used are radionuclide imaging, magnetic resonance imaging (MRI), and lymphography.
Pathologic examination
Excision biopsy of diseased lymph nodes
Rapidly growing, full, and tough enlarged lymph nodes are selected and completely excised, avoiding extrusion, and after incision, a lymph node print is made on a slide, which is then placed in a fixative solution.
Lymph node smear staining for cytopathological morphology, fixed lymph nodes after sectioning for HE staining and immunohistochemical staining, some patients need to carry out genetic and molecular pathology testing (such as second-generation sequencing, etc.).
Avoid fine needle aspiration cytology [3].
Bone marrow examination
Bone marrow examination includes bone marrow smear, flow cytometry and bone marrow biopsy.
Bone marrow tests tend to be normal in the early stages of Hodgkin’s lymphoma lesions, and R-S cells can be found on bone marrow smears in a small percentage of patients, and bone marrow biopsy reveals a higher rate of R-S cell positivity than smears, ranging from 9% to 22% [5].
R-S cells are a characteristic cell of Hodgkin’s lymphoma, and microscopically show up as huge binucleated cells, round, oval, renal or irregular.
Staging.
Staging of malignant tumors helps to rationally select treatment options, correctly evaluate efficacy, and judge prognosis.
Before staging lymphoma, it is first necessary to make a diagnosis of lymphoma and a classification and typing diagnosis based on histopathological examination results [7].
After clear typing, the lymphoma is then staged according to the 2014 Lugano staging system. Among them, stages I-IV were differentiated according to the extent of lymph node lesions, with the spleen and the lymphoid tissue of the Circle of Weiss recorded as a lymph node region, respectively. This description focuses on the early stages, and the remaining stages can be found in the Lymphoma Glossary.
Stage I: invasion of a single lymph node region (I) or focal single extranodal organ (IE).
Stage II: invasion of two or more groups of lymph nodes on the same side of the diaphragm (II) or focal single extranodal organ and its regional lymph node invasion, with or without invasion of other lymph node regions on the same side of the diaphragm (IIE).
Differential diagnosis
The early differential diagnosis of lymphoma consists of differentiating lymphoma from other diseases with similar symptoms and Hodgkin’s lymphoma from non-Hodgkin’s lymphoma.
Differentiating lymphoma from diseases that can cause fever symptoms
Lymphoma with fever as its main manifestation must be differentiated from tuberculosis, sepsis, connective tissue disease, and necrotizing lymphadenitis, and ultimately requires pathology to confirm the diagnosis.
Periodic fever of lymphoma is of diagnostic significance, usually without obvious triggering factors, and may be accompanied by painless lymph node enlargement and skin itching.
Tuberculous fever is characterized by a low-grade afternoon fever, which may be accompanied by cough and chest pain, with tuberculous foci visible on imaging and a positive tuberculin test.
Sepsis often has triggering factors such as bacterial infection, persistent high fever, elevated neutrophils, and pathogenic bacteria can be cultured in the blood.
Connective tissue disease often has inflammatory changes in joints and skin, elevated serum immune-related proteins, and positive autoantibodies.
Lymphadenitis is often characterized by foci of infection and enlarged lymph nodes with acute phase symptoms such as redness, swelling, heat, and pain. After the acute phase, the lymph nodes shrink and the pain disappears.
Differentiation of lymphoma and lymph node enlargement related diseases
Enlarged lymph nodes should be differentiated from lymphadenopathy secondary to infectious, immunologic, and neoplastic diseases, and ultimately require pathologic confirmation of the diagnosis.
Tuberculous lymphadenitis is mostly confined to the sides of the neck and may be fused with each other, adhering to the surrounding tissues, and forming sinus tracts in advanced stages due to softening and ulceration. Mycobacterium tuberculosis is seen in lymph node biopsy.
Lymphadenitis is mostly characterized by foci of infection and enlarged lymph nodes with acute phase symptoms such as redness, swelling, heat and pain. After the acute phase, the lymph nodes shrink and the pain disappears. In chronic lymphadenitis, the lymph nodes are usually enlarged 0.5 to 1.0 centimeter, softer, flatter, and more mobile.
Nodular disease is most common in adolescents and middle-aged people, mostly invades the lymph nodes, can be accompanied by multiple lymph node enlargement, commonly seen in symmetric enlargement of hilar lymph nodes, or with paratracheal and supraclavicular lymph node involvement, lymph nodes are mostly within 2 cm in diameter, the texture is usually hard, and can be accompanied by prolonged low-grade fever.
Autoimmune-related lymph node enlargement is often accompanied by other systemic manifestations, such as arthropathy, cutaneous lupus, and positive autoantibodies in serum.
Tumor lymph node metastasis often has the manifestation of the primary lesion, lymph nodes can be fused with each other to form a mass, and lymph node biopsy can help to differentiate.
Differentiation of Hodgkin’s lymphoma and non-Hodgkin’s lymphoma
Hodgkin’s Lymphoma Non-Hodgkin’s Lymphoma
Confined to a specific group of lymph nodes often spreads to more than one group of lymph nodes and has a multicentric origin.
Confined to a specific group of lymph nodes
Often spreads to more than one group of lymph nodes, multicenter origin
Spreads in an orderly fashion to neighboring lymph nodes, often in jumps, tends to involve both mesenteric lymph nodes and Waldeyer’s ring
Spreads in an orderly fashion to neighboring areas
Often spreads in a jumping pattern, tends to involve mesenteric lymph nodes and Waldeyer’s ring simultaneously
Infrequent involvement of extranodal sites Frequent involvement of extranodal sites
Infrequent involvement of extranodal sites
Often involves extranodal sites
Often diagnosed in the early stages of the disease Often diagnosed in the advanced stages of the disease
Often diagnosed in the early stages of the disease
Often diagnosed in the advanced stages of the disease
Pediatric patients often have good histology Pediatric patients often have high-risk histology
Pediatric patients often have good histologic types
Pediatric patients often have high-risk histologies
Treatment
Aim of treatment: Strive to achieve long-term remission and tumor eradication through timely and regular treatment.
Treatment principle: according to the specific condition, choose individualized comprehensive treatment, and the overall treatment is mainly based on drug therapy.
Hodgkin’s lymphoma
Hodgkin’s lymphoma is the first malignant tumor that can be cured with chemotherapy [1].
Currently, it is believed that the optimal treatment regimen for early-stage (stage I and II) Hodgkin’s lymphoma is a 4-6 cycle ABVD regimen (adriamycin, bleomycin, vincristine, and dacarbazine) combined with irradiation of the affected area.
The drugs in the ABVD regimen may have some toxic effects on the ovaries and testes during treatment. Therefore, patients need to consult their physicians about fertility preservation measures before receiving chemotherapy with the ABVD regimen.
Although this regimen is less likely to cause secondary tumors, regular follow-up is still required [4,8].
Non-Hodgkin’s lymphoma
The tendency of non-Hodgkin’s lymphoma to occur in multiple centers dictates that its treatment strategy should be based on chemotherapy [4-5,9].
The combination of chemotherapy as the mainstay of treatment and chemoradiotherapy for
Inert lymphoma
B-cell inert lymphomas include small lymphocytic lymphoma, lymphoplasmacytic lymphoma, marginal zone lymphoma, and follicular lymphoma, etc. T-cell inert lymphomas refer to mycosis fungoides/Sézary syndrome.
Inert lymphoma develops slowly and chemotherapy and radiotherapy are effective but do not resolve easily. Survival after stage I and II radiotherapy or chemotherapy can be up to 10 years, and some patients have spontaneous tumor regression, so the palliative care principle of watch and wait can be implemented. If the disease progresses, then radiotherapy or chemotherapy will be given.
Small lymphocytic lymphoma: there is no cure and most patients with this disease are elderly.
A regimen consisting of fludarabine in combination with cyclophosphamide and rituximab is usually used in younger patients who are suitable for chemotherapy.
Nitrogen mustard phenylbutyrate is given orally and has fewer side effects, so it is mostly used in older patients.
Marginal zone lymphoma: Patients may present with multiple extranodal lesions, which are sometimes cured by local radiation therapy.
Asymptomatic patients may be monitored closely without antilymphoma therapy until symptoms develop.
Gastrointestinal mucosa-associated lymphoid tissue lymphomas that do not respond to anti-Helicobacter pylori therapy may be treated with chemotherapy regimens such as radiotherapy, rituximab alone or in combination with COP or CHOP.
Follicular lymphoma: About 5% to 15% of patients have limited disease (stage I or II) at diagnosis, with a 10-year disease-free survival rate of about 50% and an overall survival rate of about 60% to 70%. 30% to 50% of patients will convert to a more aggressive type, and this group of patients usually has a poorer prognosis.
Asymptomatic patients are usually treated with a “watch and wait” strategy.
Patients who develop systemic symptoms, progressive lymph node enlargement, splenomegaly, pleural and abdominal fluid, or hematocrit usually require treatment.
For elderly patients who cannot tolerate chemotherapy, rituximab monotherapy can be used with an objective efficacy rate of up to 50%.
Rituximab in combination with a chemotherapy regimen such as COP or CHOP may further enhance efficacy.
Mycosis fungoides/Sessery syndrome: Cutaneous radiotherapy is curative for limited lesions.
Early-stage patients (lesions <10% of body surface area) are usually treated with topical skin therapy, including ultraviolet radiation, and topical hormones.
Pharmacologic therapy includes: interferon-alpha, vitamin A analogs, monoclonal antibodies, histone deacetylase inhibitors, and conventional chemotherapeutic agents.
Aggressive Lymphoma
Aggressive lymphomas are more rapidly progressive, more malignant, and relatively more difficult to treat than inert lymphomas.
B-cell aggressive lymphomas include primitive B-cell lymphoma, primitive immune cell lymphoma, condyloma, diffuse large B-cell lymphoma, and Burkitt’s lymphoma.
T-cell aggressive lymphomas include primitive T-lymphocyte lymphoma, angioimmunoblastic T-cell lymphoma, mesenchymal large-cell lymphoma, and peripheral T-cell lymphoma anaplastic type.
Aggressive lymphoma should be treated with chemotherapy regardless of the stage, and for those with residual mass from chemotherapy, localized huge mass, or central nervous system involvement, expanded irradiation (25Gy) with local radiotherapy is feasible as a supplement to chemotherapy.
CHOP regimen is the standard treatment for aggressive non-Hodgkin’s lymphoma.CHOP regimen is every 3 weeks as 1 course of treatment, and chemotherapy regimen should be changed if remission cannot be achieved in 4 courses of treatment. Complete remission is followed by 2 courses of consolidation, but not less than 6 courses of chemotherapy. The 5-year disease-free survival rate of this regimen is 41% to 80%.
For patients with diffuse large B-cell lymphoma, the rituximab in combination with CHOP regimen is the current standard of care. 6 courses of rituximab in combination with a CHOP-like regimen is the optimal regimen for younger patients with a good prognosis of diffuse large B-cell lymphoma as well as for older patients.
Some angioimmunoblastic T-cell lymphomas and Burkitt’s lymphoma progress more rapidly and should be treated with intense chemotherapy regimens.
Chemotherapy regimens consisting of high-dose cyclophosphamide are curative for Burkitt’s lymphoma.
Histone deacetylase inhibitors are targeted antitumor agents whose first indication is relapsed and refractory peripheral T-cell lymphoma, with a clinical benefit rate of more than 50% in patients and significantly prolonged survival.
Biological Therapy
Monoclonal antibodies
The majority of non-Hodgkin’s lymphomas are of the B-cell type, with 90% expressing CD20, and can be treated with CD20 monoclonal antibodies (e.g., rituximab).
The lymphocyte-dominant type of Hodgkin’s lymphoma highly expresses CD30 and can be treated with CD30 monoclonal antibodies (e.g., vibritumomab).
Interferon
Interferon has been shown to have a partial remission effect in mycosis fungoides, among others.
Anti-Helicobacter pylori (Hp) drugs
Gastric mucosa-associated lymphoid tissue lymphoma has been treated with anti-Hp therapy, resulting in improvement of symptoms and disappearance of lymphoma in some patients.
CAR-T therapy
Cellular immunotherapy, i.e. chimeric antigen receptor T-cell immunotherapy (CAR-T therapy), has achieved certain efficacy in relapsed refractory B-cell lymphoma.
Surgery
If there are indications for splenectomy in patients with hypersplenism, splenectomy can be performed to improve blood picture and create favorable conditions for subsequent chemotherapy.
Prognosis
The cure of early stage lymphoma is relatively ideal, the 5-year survival rate of Hodgkin’s lymphoma has exceeded 90%, and non-Hodgkin’s lymphoma may also survive for 10 years after early comprehensive treatment.
Cure
The treatment of Hodgkin’s lymphoma has made great progress and is one of the tumors that can be cured by chemotherapy. The 5-year survival rate of stage I and II is more than 90%, and its prognosis is related to tissue type and clinical stage. The 5-year survival rate of Chinese patients with early stage classic Hodgkin’s lymphoma has reached 96.7% [3].
The cure rate of non-Hodgkin’s lymphoma varies widely. Inert lymphoma develops slowly, chemotherapy and radiotherapy are effective, and survival can be up to 10 years after stage I and II radiotherapy or chemotherapy. Aggressive lymphomas have lower cure rates. Specific cures are related to risk groupings, as detailed in the Prognostic Factors section.
Prognostic Factors
Prognostic factors are factors that have an impact on a patient’s overall survival and quality of life.
Hodgkin’s lymphoma
There is no consensus on the prognostic factors for Hodgkin’s lymphoma.
According to the National Comprehensive Cancer Network (NCCN), poor prognostic factors in the early stages of Hodgkin’s lymphoma include the following [3].
Erythrocyte sedimentation rate (ESR) ≥50 mm/hour or ≥30 mm/hour with B symptoms.
Mass maximum diameter/thoracic cavity maximum diameter >0.33, or mass diameter >10 cm.
Number of involved lymph node regions >3.
Higher age is also one of the poor prognostic factors, with different age thresholds defined in different countries, and the prognosis is mostly considered to be worse for those over 40 or 50 years of age.
Non-Hodgkin’s lymphoma
Non-Hodgkin’s lymphoma is classified into 4 categories of low risk, low intermediate risk, high intermediate risk, and high risk according to the number of International Prognostic Index (IPI), i.e., age greater than 60 years old, stage III or IV, more than 1 extranodal lesion, need for bed rest or living in the care of other people, and elevation of serum lactate dehydrogenase as the 5 poor prognostic factors [9].
The prognosis of non-Hodgkin’s lymphoma is relatively good in the early stages, and patients can survive for a long time by radiotherapy, while a poor prognosis is suggested if the age is more than 60 years old, poor physical status, elevated serum lactate dehydrogenase, or more than one extra-lymph node lesion.
Survival data for different prognostic subgroups for early-stage non-Hodgkin’s lymphoma are not available and can be referred to for overall survival data.
Prognosis Number of IPIs 2-year survival 5-year survival
Low-risk 0 to 184% 73%
Low-risk
0 to 1
84 percent
73 percent
Low to medium risk 266% 50%
Low to medium risk
2
66 percent
50 percent
High Medium Risk 354% 43%
High Medium Risk
3
54 percent
43 percent
High risk 4-534% 26%
High risk
4 to 5
34 percent
26 percent
Daily routine
Early stage lymphoma patients should pay attention to scientific diet, regular work and rest, moderate exercise, and adjust the mind. The efficacy of chemotherapy is obvious, but certain adverse reactions may occur, which should be monitored and coped with in time.
Daily Management
Diet management
There are no special contraindications in the diet of early stage of lymphoma, in principle, it is necessary to replenish sufficient calories, proteins, carbohydrates, rich minerals and vitamins and moderate amount of fats to meet the needs of disease recovery.
Eat more protein-rich food, such as eggs, milk, lean meat, fish, etc., and also supplement fat nutrition.
It is recommended to avoid eating only refined rice and white flour, and add coarse grains such as corn, cereals and miscellaneous beans as appropriate.
More vitamin-rich fresh fruits and vegetables can be consumed to replenish the minerals and vitamins needed by the body.
It is recommended to eat less or no raw, cold, stimulating, pickled, fried and deep-fried foods, such as salted fish, bacon, fried chicken and chili peppers.
Life management
The living environment should be kept clean, with adequate ventilation, sufficient sunlight, and suitable temperature and humidity. Disinfect rooms regularly to avoid infection.
Maintain good hygiene and cleanliness, gargle with saline solution after meals and before bedtime every day, and use a soft-bristled toothbrush. Brushing and flossing should be gentle to avoid bleeding gums.
Exercise moderately, but pay attention to prevent accidental bodily injury, especially for those who are prone to bleeding, avoid excessive activities and trauma.
Psychological support
The early cure rate of lymphoma is relatively high, such as the early 5-year survival rate of Hodgkin’s lymphoma can be as high as more than 95%, and the early cure of inert lymphoma in non-Hodgkin’s lymphoma is also relatively ideal. Patients should have confidence in overcoming the disease.
Family members should give more help and support to the patients, so that they can face the treatment positively with a good mindset.
Disease monitoring
Patients should pay attention to whether their symptoms have worsened or alleviated, or whether new symptoms have appeared. If there is any abnormality, it is recommended to consult a doctor in time. However, there is no need to be over-stressed. Maintaining a good mood and mindset cannot be replaced by medication.
Follow-up Review
Overall review recommendations
Conduct a comprehensive assessment after completing the full course of treatment, and use this as a baseline for subsequent follow-up visits at regular intervals.
General Follow-up Frequency
Curable types (e.g. diffuse large B-cell lymphoma, Hodgkin’s lymphoma, etc.): review every 3 months for the first 2 years after completion of treatment, every 6 months thereafter, and annually after 5 years.
Incurable types (e.g., low-grade follicular lymphoma, etc.): review is recommended every 3 to 6 months up to lifelong.
Detailed follow-up plan
In long-term survivors, secondary tumors, cardiovascular disease, hypothyroidism and infertility are the most serious delayed adverse events, with an increased incidence over time.
Screening program follow-up plan
Medical history, physical examination, blood routine, platelets, blood sedimentation, biochemical tests are reviewed every 3 to 4 months for the first 2 years; every 6 months for the third to fifth years; and annually after 5 years.
Medical history, physical examination, blood count, platelets, blood sedimentation, biochemical tests
Review every 3 to 4 months in the first 2 years; every 6 months in the 3rd to 5th year; annually after 5 years.
If CT is not available, chest X-ray can be chosen. The examination should be repeated every 3 months in the first 2 years, every 6 months in the third to fifth years, and annually after 5 years.
When CT is not available, chest X-ray is an option.
Review every 3 months for the first 2 years; every 6 months for the third to fifth years; and annually after 5 years.