What Is a Malignant Lymphoma?

Malignant lymphoma (ML) is a general term for a group of malignant tumors that originate in the lymphoid hematopoietic system. Its main clinical manifestation is painless lymphadenopathy, which can affect all tissues and organs throughout the body. Lymphoma patients may develop systemic symptoms such as fever, night sweats, weight loss, and skin itching before or at the same time as lymphadenopathy.

Basic Information

English name

malignant lymphoma

Visiting department

Oncology, Hematology

Common locations

Lymph nodes or tissues or organs outside the lymph nodes

Common symptoms

Swollen lymph nodes, swelling of the head and neck, cough, difficulty breathing, difficulty swallowing, etc.

Contagious

no

Causes of malignant lymphoma

Lymphoma is a disease caused by abnormal differentiation and proliferation of immune-active cells at different developmental stages under the combined action of internal and external factors. The etiology of lymphoma has not yet been fully elucidated, and its occurrence and development involve many aspects such as genetic, viral and other pathogen infections, radiation, chemical and other physical and chemical factors, and immune status.

Clinical manifestations of malignant lymphoma

ML is a large class of tumors with considerable heterogeneity. Although it occurs in lymph nodes, due to the distribution of the lymphatic system, lymphoma is basically a systemic disease that can invade almost any tissue and organ in the body. Therefore, the clinical manifestations of ML not only have certain common characteristics, but also have great differences according to different pathological types, affected sites and areas.

Local performance

(1) Lymph node enlargement is the most common and typical clinical manifestation of lymphoma. Lymphomas are usually characterized by painlessness, smooth surface, and movement. The texture of the palate is tough, full, and uniform. It is active early, isolated or scattered in the neck, axillae, and groin. In the later stage, it fuses with each other. Skin adhesions, inactivity, or ulcers. HL mostly invades superficial lymph nodes first, and is more common in neck, supraclavicular, and axillary lymph nodes, but is rare around sacral vessels, groin, femoral triangle, and pulley lymph nodes. It can also invade the mediastinum, retroperitoneum, and mesentery. Deep lymph nodes. HL lymph node involvement is mostly continuous, invading adjacent nodes in turn. NHL first showed that more than half of the patients with superficial lymph nodes were involved. The affected lymph nodes were skipping and had no regular pattern. Extranodal lymph tissues or organs were also more common.

(2) Waldeyer's ring lesions, also known as pharyngeal lymph rings, is a circular lymphoid tissue located in the openings of the respiratory tract and digestive tract, including the nasopharynx, tongue base, bilateral tonsils and soft palate. In this structure, the mucosa and submucosa have abundant lymphoid tissues that can play an immune defense function in the upper respiratory tract and digestive tract. Approximately more than half of extranodal lymphomas that originate in the head and neck occur in the Wechsler ring. The NHL, which originates in Wechsler's ring, occurs in 40% to 79% of the tonsils. It is the most common primary site, followed by the nasopharynx, which is less common in the base of the tongue and soft palate.

(3) Nasal lesions Most of the primary nasal lymphomas are NHL, and the main pathological types include nasal NK / T-cell lymphoma and diffuse large B-cell lymphoma.

(4) Thoracic lesions Mediastinal lymph nodes are the predominant sites of ML. They are more common in primary mediastinal (thymus) diffuse large B-cell lymphomas and precursor T-cell lymphoblastic lymphomas in HL and NHL. Swollen lymph nodes are most often located in the mediastinum and anterior mediastinum, with bilateral mediastinal involvement. Most patients have no obvious symptoms at the initial stage. As the tumor gradually increases, they can compress the nearby trachea, esophagus, veins, etc., causing cough, dyspnea, and difficulty swallowing. If the disease progresses rapidly, superior vena cava syndrome can occur. Swelling of the head and neck, dyspnea, inability to lie flat, angulation of superficial veins of the neck and chest, etc. When the pleura is invaded, it appears as a pleural mass or nodule, and pleural effusion may appear. The effusion is inflammatory or bloody, and naive lymphocytes and lymphoma cells can be found. There are round, quasi-round, or lobular shadows on the chest X-ray. The progression of the disease can compress the bronchus and cause atelectasis, and the central necrosis of the tumor can form a cavity. In addition, some lung lesions are manifested as diffuse interstitial changes. At this time, clinical symptoms are obvious. Cough, sputum, shortness of breath, dyspnea, and fever may be caused by secondary infection.

(5) Myocardial and pericardial lesions ML can invade myocardium and pericardium. Pericardial invasion can be expressed as pericardial effusion, myocardial invasion as myocardial disease, arrhythmia, abnormal electrocardiogram, etc. can occur.

(6) Abdominal and pelvic lesions Lymph nodes of the abdomen and pelvic cavity are also common sites of lymphoma invasion, including retroperitoneal, mesenteric, popliteal and other sites. Simple lymphadenopathy usually has few local symptoms and is not easy to detect early in clinical practice. Splenomegaly and hepatomegaly are common clinically, and the spleen is the most common site of HL invasion in HL. 60% of HL patients with splenomegaly were confirmed to have spleen invasion by pathology. People with spleen invasion may have liver invasion, while those with liver infestation alone are rare. The incidence of liver invasion is 3% to 24%, and it is mostly secondary to spleen invasion. The gastrointestinal tract is the most common site of extranodal involvement in NHL, accounting for about 50% of all extranodal lymphomas. Gastrolymphomas are mostly asymptomatic in the early stages, after which indigestion, fullness and discomfort, and epigastric mass may occur. Small bowel lymphoma can manifest as abdominal pain, abdominal mass, and is prone to emergencies such as intestinal obstruction, intestinal perforation, and bleeding.

(7) skin lesions ML can be primary or secondary skin invasion, more common in NHL. Patients with ML may have a series of non-specific skin manifestations, skin lesions are polymorphic, erythema, blister, erosion, etc. Patients with advanced ML have low immune function, and skin infections often rupture and exudate, resulting in systemic scattered skin thickening and desquamation.

(8) Bone marrow invasion of bone marrow lesions is manifested as bone marrow invasion or combined with leukemia, which is one of the advanced manifestations of the disease, and most of them are NHL.

(9) manifestations of the central nervous system Most primary central nervous system lymphomas (PCNSL) are single lesions (approximately 70%) and superficial lesions at the time of diagnosis, and in the late stage of the disease, they are usually extensive multifocal lesions. Scattered. Typical lesions are located in the deep structures of the ventricle, and they easily involve the corpus callosum, basal nodes, and thalamus. Primary to the spinal cord and cerebrospinal cord is rare, but it is more common to this end. Common clinical symptoms are the same as other intracranial tumors. Symptoms of increased cranial pressure, cranial nerve dysfunction, and seizures are common due to tumor infiltration or compression.

(10) Other MLs can also be primary or secondary to the brain, extradural, testis, ovary, vagina, cervix, breast, thyroid, adrenal gland, posterior orbital tissue, larynx, bone, and muscle soft tissue, etc. The clinical manifestations are complex Diversity, attention should be paid to identification.

2. Whole body performance

(1) Systemic symptoms Patients with ML may develop systemic symptoms such as fever, itching, night sweats, and weight loss before or at the same time as lymphadenopathy.

(2) Immune and blood system manifestations 10% to 20% of ML diagnosis may be accompanied by anemia, some patients may have increased white blood cell counts, platelet counts, increased erythrocyte sedimentation, individual patients may have leukemia-like reactions, and neutrophils significantly increased. . In addition, an increase in lactate dehydrogenase is associated with tumor burden. Some patients, especially advanced patients, show abnormal immune function. In B-cell NHL, the number of different monoclonal immunoglobulins can be detected in the serum of some patients.

Malignant Lymphoma Examination

1. Blood routine and blood smear

Blood routine is generally normal and may be associated with chronic anemia. HL may show thrombocytosis, increased white blood cell count, and increased eosinophils; NHL invaded the bone marrow may cause anemia, decreased white blood cells and platelets, and lymphoma cells in peripheral blood.

2. Bone marrow smear and biopsy

HL rare bone marrow involvement. NHL invades the bone marrow. Lymphoma cells can be seen in the bone marrow smear. The cell volume is large, the chromatin is rich, gray-blue, the shape is obviously abnormal, and the "tailing phenomenon" can be seen. Lymphoma cells 20% are lymphoma leukemia; bone marrow biopsy shows lymphoma cell aggregation and infiltration. In some patients, bone marrow smears show increased hemophagocytosis and hemophagocytosis, which are more common in T-cell lymphoma.

3. blood biochemistry

Increased lactate dehydrogenase (LDH) is related to tumor burden and is an indicator of poor prognosis. HL may be accompanied by increased ESR and increased alkaline phosphatase (ALP).

4. Cerebrospinal fluid examination

Patients with stage III / IV invasive NHL, or those with central nervous system symptoms, need to undergo cerebrospinal fluid examination. Cerebrospinal fluid examination of patients with central nervous system involvement shows increased cerebrospinal fluid pressure, increased protein, increased cell numbers, and mononuclearity. Pathological examination or flow cytometry examination can find lymphoma cells.

5. Histopathological examination

The basic pathological morphological change of HL is to see diagnostic RS cells and their variant cells in a mixed proliferation background with multiple non-tumor inflammatory cells. The immunohistochemical characteristics of classical HL are: CD15 +, CD30 +, CD25 +; the immunohistochemical characteristics of nodular lymphocyte-based HL are: CD19 +, CD20 +, EMA +, CD15-, CD30-. The pathological and morphological changes of NHL were the disappearance of normal lymph node structure, unclear demarcation of cortex and medulla, lymphatic sinus and lymphoid follicles or lymph node capsule invasion, and the entire lymph nodes were diffuse and replaced by lymphocytes with different degrees of differentiation. According to different pathological types, there are their own unique pathological manifestations and immunophenotypes.

6. T cell receptor (TCR) or immunoglobulin (Ig) gene rearrangement

Human peripheral B and T cells are characterized by the presence of antigen receptor genes that encode the amino acid sequences of the polypeptide subunits that make up Ig and TCR. The rearrangement of these antigen receptor genes is the main molecular diagnostic marker of ML. Clonal gene rearrangement has important reference value for distinguishing benign and malignant lymphocyte hyperplasia.

Diagnosis of malignant lymphoma

ML has various clinical manifestations, which can be manifested as painless lymphadenopathy, but also can be manifested as other system involvement or systemic symptoms. At present, there is no effective screening method for lymphoma, and educating the public to raise awareness of cancer prevention is an important method for early detection of disease. When clinically suspected of lymphoma, a lymph node biopsy or puncture or biopsy of the affected tissue / organ should be performed for pathological examination and clear pathological diagnosis. Those who have the conditions should also carry out cytogenetic tests, the purpose is to make the pathological type as clear as possible.

Malignant Lymphoma Treatment

Because lymphomas are highly heterogeneous, their treatments are also very different. Lymphomas of different pathological types and stages differ greatly in terms of treatment intensity and prognosis. There are several treatment methods for lymphoma, but the specific treatment plan should be formulated according to the actual situation of each patient.

Radiation therapy

Certain types of lymphoma can be treated with radiotherapy alone at an early stage. Radiotherapy can also be used for consolidation after chemotherapy.

2. Chemotherapy

Lymphoma chemotherapy often uses a combination chemotherapy regimen, which can be combined with targeted drugs and biological agents. In recent years, chemotherapy for lymphoma has been greatly improved, and the long-term survival rate of many types of lymphoma has been significantly improved.

3. Hematopoietic stem cell transplantation

For patients under 60 years of age with adverse prognostic factors, if they can tolerate high-dose chemotherapy, autologous hematopoietic stem cell transplantation may be considered. Hematopoietic stem cell transplantation can also be considered in patients with bone marrow involvement.

4. Surgery

Limited to tissue biopsy or management of complications. For patients with hypersplenism without contraindications, splenectomy can be performed for those who have indications for splenectomy to create favorable conditions for future treatment.

Prognosis of malignant lymphoma

Multiple studies have shown that the prognosis of ML is related to the following factors: age; mass size (> 5cm); extranodal invasion; spleen invasion; erythrocyte sedimentation; B symptoms; High; staging; pathological types, etc.

The prognosis of HL is closely related to the pathological type and clinical stage. The following adverse factors will affect the prognosis of patients with limited period of time. The adverse prognostic factors proposed by the German Hodgkin's Lymphoma Research Group (German Hodgkinstudygroup, GHSG) include: huge mass (maximum lateral diameter of chest X-ray mass> 1/1 3) Or mediastinal mass at T5-6 level> 35% of the internal diameter of the thorax, or any mass> 10cm on CT); ESR without B symptoms 50mm / h; ESR with B symptoms 30mm / h; more than 3 sites of invasion; extranodal invasion. The adverse prognostic factors proposed by the European Organization for Research and Treatment of Cancer (EORTC) include: huge mass; ESR without B symptoms 50mm / h; ESR with B symptoms 30mm / h; Invasion Sites 4; Age 50 years. Currently, the international prognosis score (internationalprognosticscore, IPS) is used to determine the prognosis of patients with advanced stages, including: albumin <40g / L; hemoglobin <105g / L; male; age 45 years; stage IV disease; leukocytes Hyperplasia (WBC15 × 10 ⁹ / L); lymphocyte decrease (the total number of lymphocytes is less than 8% of the total number of white blood cells and / or the total number of lymphocytes is <0.6 × 10 / L). Each item is 1 point, and the progression-free survival rates for groups 0, 1, 2, 3, 4, and 5 are 84%, 77%, 67%, 51%, and 42%, respectively. Progressive survival rate was 8%. According to the pathological type, the prognosis of lymphocyte is the best, and the type of lymphocyte depletion is the worst; nodular sclerosis and mixed cell type are in between.

The prognosis of NHL is also closely related to the pathological type and stage. Diffuse large cell lymphoma (DLBCL) is the most common ML in adults. The international prognostic index (IPI) can be used to determine the prognosis of patients with aggressive lymphoma represented by DLBCL and guide the choice of treatment options. IPI was scored based on patient age, general status, the Eastern Collaborative Oncology Group (ECOG) score, clinical stage, number of extranodal affected sites, and whether lactatedehydrogenase (LDH) was elevated. According to the score, it is divided into four groups: low risk (0 or 1 point), low to medium risk (2 points), medium to high risk (3 points), and high risk (4 or 5 points). The five-year overall survival rate after treatment is 73%, 51%, 43% and 26%. The age-adjusted International Prognostic Index (ageadjustedIPI, aaIPI) is developed for patients younger than 60 years of age. The difference from IPI is that age and the number of extranodal affected sites are not independent poor prognostic factors. The corresponding scores for the intermediate-risk group, intermediate-high-risk group, and high-risk group were 0, 1, 2, and 3, and the 5-year overall survival rates were 83%, 69%, 46%, and 32%, respectively. The adjusted IPI can also be used for indolent lymphoma. For example, the prognosis of follicular lymphoma is evaluated using the follicular lymphoma international prognosis index (folicullarlymphomaIPI, FLIPI) score.

Table 1. NHL's International Prognostic Index (IPI)

Risk factors *	All patients	Age> 60 years
		LDH> Normal
		General condition (ECOG) 2 grade
		Clinical Stage (AnnArbor) III / IV
		Number of extranodal organ invasions> 1
	60 years	LDH> Normal
		General condition (ECOG) 2 grade
		Clinical Stage (AnnArbor) III / IV
Divided into 4 groups according to risk factors:
Degree of danger		Risk factor score
		All patients	Patients 60 years
Low risk group		0 or 1	0
Low-risk group		2	1
High-risk group		3	2
High-risk group		4 or 5	3

*: 1 point for each risk factor

Table 2 Relationship between IPI score and 5-year overall survival

Danger group	All patients (%)	60 years old (%)	> 60 years old (%)
Low risk	73	83	56
Low to medium risk	53	69	44
Medium to high risk	43	46	37
High risk	26	32	twenty one

Table 3 Follicle Lymphoma International Prognosis Index (FLIPI) Score and 10-year Overall Survival

FLIPI score	Risk factor score	10-year total survival (%)
Low risk group	0, 1	71
Intermediate Risk Group	2	51
High-risk group	3-5	30

Risk factors include: age 60 years; staging: stage III / IV; hemoglobin level: L; LDH: abnormal; lymph node area:> 4. 1 point for each risk factor, divided into three groups based on risk factors