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Lymphoma
Clinical manifestations, laboratory tests, diagnosis, differential diagnosis, clinical staging and treatment of lymphoma (Hodgkin lymphoma HL, non-Hodgkin lymphoma NHL)
Edited at 2023-07-28 17:46:42
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Lymphoma
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Lymphoma
Summary
definition
Refers to malignant tumors derived from lymphocytes and their precursor cells
Including: lymphoma, lymphocytic leukemia, hairy cell leukemia and plasma cell tumors, etc.
Primary in lymph nodes or lymphoid tissue
The main clinical manifestations are painless and progressive lymphadenopathy.
Its occurrence is mostly related to lymphocyte proliferation during immune response. It is related to the malignant transformation of certain immune cells produced by differentiation.
Can be seen as being blocked in the differentiation process of B cells or T cells Clonal proliferation of lymphocytes at a certain stage
lymph node structure
Cause and pathogenesis
Cause
Virus
Epstein-Barr virus → Burkitt lymphoma Leukemia virus/Human T-lymphotropic virus type I HTLV-I→Adult T-cell leukemia/lymphoma HTLV-II → T-cell cutaneous lymphoma (granuloma) Kaposi sarcoma virus → body cavity lymphoma
Helicobacter pyloriHp
Gastric mucosa-associated lymphoid tissue extranodal marginal zone lymphoma (gastric MALT lymphoma)
Immunocompromised
Pathogenesis
Lymphocytes are stimulated by exogenous or endogenous antigens for a long time, resulting in a proliferative response. Due to the loss or dysfunction of T suppressor cells, lymphocytes lose normal feedback control on the proliferative response to antigen stimulation, resulting in unrestricted proliferation.
pathology
Typical characteristics
① The normal follicular structure of the lymph node is destroyed by a large number of abnormal lymphocytes or tissue cells, and the capsule and surrounding tissues are also invaded
②The division index of abnormal cells increases
Classification
By histopathology
Hodgkin lymphoma HL
Non-Hodgkin LymphomaNHL
NHL
Cell source: 90% B
HL: Approximately 100% B
Incidence rate (proportion of lymphoma): 80~90%
HL: 10~20%
Prevalent age: the elderly (60)
HL: Two peaks (15~27, >50)
More men than women
HL: More males than females
First symptom: painless cervical or supraclavicular lymphadenopathy
HL: Same as left
Primary lesion: lymph node (2/3), extranodal tissue (1/3)
HL: lymph node (90%)
Transfer method: jump transfer
HL: transfer sequentially
②
Non-Hodgkin LymphomaNHL
Types
International Work Classification (IWF, 1982)
Common subtypes of WHO classification
B cell
Diffuse large B-cell lymphoma DLBCL
The most common, accounting for 35%-40%
aggressive lymphoma (can develop by laziness)
Divided into germinal center type and activated cell type
Anti-CD20 monoclonal antibodies can significantly improve the prognosis of these patients
prognosis
Rituximab improves outcomes
marginal zone lymphoma MZL
The marginal zone is the area between lymphoid follicles and follicular mantles
indolent lymphoma
Classification according to affected parts
Extranodal mucosa-associated lymphoid tissue marginal zone lymphoma MALT
gastric MALT
non-gastric MALT
Splenic B-cell marginal zone lymphoma
Node marginal zone lymphoma/monocytoid B-cell lymphoma
mantle cell lymphoma MCL
aggressive lymphoma
Mantle B cells derived from extrafollicular CD5 and CD20
chromosomal translocation
Often t(11;14), specifically expressing CyclinD1
follicular lymphoma FL
indolent lymphoma
Originating from the germinal center,
The response to chemotherapy is good, but it cannot be cured. The disease course is long, relapses repeatedly or becomes aggressive.
chromosomal translocation
t(14;18), high expression of Bcl-2 (anti-apoptotic effect)
clinical manifestations
Inguinal lymph nodes are often involved, often involving the spleen
prognosis
Prognosis is better
30% transform into DLBCL, often accompanied by p53 gene mutations, and the prognosis becomes worse
Burkitt Leukemia/LymphomaBL
highly invasive
When it invades the blood and bone marrow, it is called ALL L3 type.
Epidemiology
Affects children and is related to Epstein-Barr virus
In endemic areas (Africa), the jaw is often involved, and peripheral lymph nodes and spleen are generally not involved.
In non-endemic areas, lesions mainly involve the terminal ileum and abdominal viscera
chromosomal translocation
t(8;14)
Pathological characteristics
tumor cells
They are medium-sized cells with diffuse growth and uniform shape. Apoptosis and necrosis are common.
The cytoplasm is sparse, vacuolated, and basophilic. The nucleus is large, round or oval, with fine chromatin, often with 2 to 3 obvious nucleoli, and mitotic figures are common.
around
Reactive proliferating macrophages with rich and translucent cytoplasm are distributed among cancer cells. Formation of "starry sky" phenomenon/starry sky image
prognosis
Chemotherapy is more effective
T-cell
Anaplastic large cell lymphoma ALCL
aggressive lymphoma
More common in children
Tumor cells resemble R-S cells
Rapid clinical development
Peripheral T-cell lymphoma (unspecified) PTCL
aggressive lymphoma
Originates from mature (postthymic) T cells and NK cells
Mycosis fungoides/Sézary syndrome MF/SS
indolent lymphoma
Mycosis fungoides is common
Pautrier: accumulation of cancer cells in the epidermis
Sezary cells: cancer cells with gyral nuclei in the patient's peripheral blood
Proliferated cells are mature helper T cells
prognosis
Those confined to the skin have a better prognosis
Those who spread to the blood and internal organs have a poor prognosis
Invasion of peripheral blood is called Sézary syndrome
angioimmunoblastic T-cell lymphoma AITL
An aggressive T-cell lymphoma originating from follicular helper T cells CD4, which is more common in the elderly.
Clinical manifestations include fever and lymphadenopathy
poor prognosis
Positive Coombs test with multistrain hyperimmune globulinemia
clinical manifestations
Features
Systemic
It can occur in any part of the body, with lymph nodes, tonsils, spleen and bone marrow being the most commonly affected areas.
Diversity
The range and degree of oppression or infiltration are different, and the symptoms caused are also different.
Epidemic characteristics
The incidence increases with age, more men than women
Except for indolent lymphomas, which generally develop rapidly
Performance
high fever
Symptoms of various organs and systems (compression and infiltration)
pharyngeal lymphatic ring
May have difficulty swallowing, nasal congestion, epistaxis, and submandibular lymph node enlargement
Chest (hilar and mediastinum most affected)
Half have pulmonary infiltrates or pleural effusion, which can cause cough, chest tightness, shortness of breath, atelectasis, and superior vena cava compression syndrome.
Gastrointestinal tract (mostly the ileum, followed by the stomach)
Clinical manifestations include abdominal pain, diarrhea and abdominal mass. Often diagnosed after surgery for intestinal obstruction or massive bleeding
liver and spleen
Hepatomegaly and jaundice are only seen in more advanced cases, and NHL originating in the spleen is less common.
kidney
kidney damage
Mainly renal enlargement, hypertension, renal insufficiency and nephrotic syndrome
Retroperitoneal lymph node enlargement can compress the ureter and cause hydronephrosis
Central nervous system lesions (mostly involving the meninges and spinal cord)
Epidural mass can cause spinal cord compression
Bone damage (thoracic and lumbar spine most common)
Bone pain, destruction of lumbar or thoracic vertebrae, spinal cord compression, etc.
About 20% of NHL patients have bone marrow involvement in the late stages and develop into lymphoma leukemia.
skin involvement
Masses, subcutaneous nodules, infiltrative plaques, ulcers, etc.
examine
Blood and bone marrow tests
Blood
The number of white blood cells is normal, accompanied by an absolute or relative increase in lymphocytes
bone marrow
Lymphoma cells can be found in bone marrow smears in some patients
When lymphoma cell leukemia occurs in the late stage, leukemia-like blood and bone marrow images may appear.
Laboratory examination
ESR
When the speed increases, it indicates the active stage of the disease.
serum lactate dehydrogenase
Elevated levels indicate poor prognosis
Serum alkaline phosphatase activity, serum calcium
Elevated levels indicate bone involvement
B-cell NHL can be complicated by hemolytic anemia with a positive or negative antiglobulin test
Film degree exam
Examination of superficial lymph nodes
B-ultrasound examination and radionuclide imaging
Mediastinal and lung examination
Chest X-ray, Chest CT
Examination of abdominal and pelvic lymph nodes
CT is the preferred method for abdominal examination
Examination of liver and spleen
CT, B-ultrasound, radionuclide imaging and MRI
PET/CT examination
Important indicators for evaluating the efficacy of lymphoma
Pathological examination
lymph node biopsy
Deep lymph nodes can be punctured under the guidance of B-ultrasound or CT
diagnosis
Confirmed
symptom
Progressive, painless lymphadenopathy
examine
For patients with progressive and painless lymphadenopathy, lymph node prints and pathological sections or lymph node aspirate smear examination should be performed
Skin biopsy and prints can be done when cutaneous lymphoma is suspected
When accompanied by an abnormal number of blood cells, increased serum alkaline phosphatase, or bone lesions, bone marrow biopsy and smears can be performed to look for R-S cells or NHL cells to understand the bone marrow involvement.
Types
Monoclonal antibodies, cytogenetics and molecular biology techniques
identify
Other lymphadenopathy diseases (tuberculous lymphadenitis)
Limited to both sides of the neck, they can fuse with each other and adhere to surrounding tissues. In the later stage, sinus tracts are formed due to softening and ulceration.
Lymphoma with fever as the main manifestation
Tuberculosis, sepsis, connective tissue disease, necrotizing lymphadenitis, and hemophagocytic lymphohistiocytosis, etc.
extranodal lymphoma
Other malignant tumors of corresponding organs
R-S cells
R-S cells can also be seen in infectious mononucleosis, connective tissue diseases and other malignant tumors, so seeing R-S cells alone cannot diagnose HL.
treat
Comprehensive treatment based on chemotherapy combined with chemotherapy and radiotherapy
The multicenter tendency of NHL makes clinical staging more valuable and The therapeutic effect of extended irradiation is not as good as that of HL
Biotherapy
Monoclonal antibodies
All CD20-positive B-cell lymphomas can be treated with CD20 monoclonal antibody (rituximab)
Interferon
It has a partial alleviation effect on mycosis fungoides, etc.
Anti-Helicobacter pylori drugs
Symptoms of some patients with gastric MALT lymphoma improved and lymphoma disappeared after anti-Helicobacter pylori treatment
CAR-T cell immunotherapy
Hematopoietic stem cell transplantationHSCT
Be applicable
Under 55 years old, with normal functions of important organs
Aggressive lymphoma with a short remission period, refractory to treatment and easy to relapse, and those with four CHOP regimens that can shrink lymph nodes by more than 3/4
Autologous or allogeneic bone marrow (or peripheral hematopoietic stem cell) transplantation
Surgical treatment
If there are indications for splenectomy in patients with hypersplenism, splenectomy may be performed
①
Hodgkin's Lymphoma HL (Hodgkin's Disease HD)
Account for 10-20%
Pathology and classification
pathology
in general
Often nodular, grayish white in cut surface, fish-like
under the mirror
inflammatory cell infiltration
Mixed infiltration of a variety of inflammatory cells (lymphocytes (mainly), plasma cells, neutrophils, eosinophils)
Tumor cells are scattered throughout
Inflammatory cell context Scattered tumor cells (R-S cells) and their variant cells
Typical R-S cells
source
Almost all HL cells are derived from B cells, and only a few are derived from T cells
Performance
Three big and one red
The cells are huge, with a diameter of 25~30 μm. The cytoplasm of the cells is rich and slightly eosinophilic or alkaline. They are binucleated or multinucleated. The nuclei are round, the nuclear membrane is thick, and there are inclusion body-like eosinophilic nucleoli, which are large and obvious, about the same size as red blood cells. There is a halo around the nucleolus
Bi-nucleated R-S cells have two nuclei arranged opposite each other, resembling the shadow in a mirror, and are called mirror-image cells.
May be accompanied by capillary proliferation and varying degrees of fibrosis
Mononuclear R-S cells (Hodgkin cells)
Same as typical R-S except single core
lacunae cells
The tumor cells are large in size, with loose chromatin in the nucleus and one or more smaller basophilic nucleoli. After being fixed with formaldehyde, the cytoplasm shrinks to the vicinity of the nuclear membrane and forms a transparent gap between the surrounding cells, as if the cells are located in a lacunae.
LP cells (popcorn cells)
The tumor cells are large in size, have multi-lobed nuclei, sparse chromatin with multiple small alkaline nucleoli, and pale cytoplasm.
Mummy cells (mummy cells)
Degenerated or apoptotic R-S cells, with condensed and densely stained nuclei and eosinophilic cytoplasm, so-called mummification
Types
Nodular lymphocyte predominant type ~ NLPHL
Epidemiology
Uncommon, accounting for 5% of HL, patients aged 30 to 50 years old, mostly men
Features
More than 95% are nodular
Microscopically, it is dominated by the proliferation of single small lymphocytes. Typical R-S cells are difficult to find, and most of them are popcorn cells with multi-lobed nuclei.
immunological phenotype
A large number of CD20⁺ small B cells, forming nodules or nodule-like structures. There are CD20⁺ neoplastic large B cells in the nodules, that is, lymphoid and tissue cells (L/H type R-S cells).
L/H type R-S cells
呈CD20⁺、CD79a⁺、bcl6⁺、CD45⁺、CD75⁺
约一半病例上皮细胞膜抗原（EMA⁺） ，免疫球蛋白轻链和重链常呈阳性，不表达CD15和CD30
EB virus infection is not seen, and the main manifestations are neck and armpit masses. The prognosis of most patients is excellent, and the ten-year survival rate reaches 80%.
Classic~ CHL, 95%
Lymphocyte-rich LR Best prognosis
Features
Accounts for 5% of classic lesions
Epstein-Barr virus infection is seen in about 40% of cases
Pathological changes
Typical R-S cells are scattered in a background dominated by mature lymphocytes.
tuberous sclerosis NS second most common
Features
It accounts for 40% to 70% of the classic type and is more common in young women. The peak age of onset is between 15 and 34 years old.
Most commonly occur in cervical, supraclavicular and mediastinal lymph nodes
EBV infection rate is low, ranging from 10% to 40%
20%-40% of RS cells usually express CD\15\30
Pathological changes
Tumor cells are "lacunar" R-S cells (lave cells)
Under light microscopy, it appears that birefringent collagen fiber bundles separate lymph nodes into nodules of varying sizes.
The diseased tissue is nodular
Eosinophils and neutrophils are often more common
mixed cell MC Most common
Features
Accounting for typically 20% to 25%, it is more likely to occur in older men and is often accompanied by EB cell infection.
Epstein-Barr virus infection is present in approximately 75% of cases
Immunohistochemistry positive for CD30, 15, PAX-5
Pathological changes
The structure of the lymph nodes is destroyed
Tumor cells are mixed with various inflammatory cells
Eosinophils, lymphocytes (mainly T cells), and fibroblasts can be seen
Both typical R-S cells and mononuclear R-S cells are common, accompanied by necrosis
Lymphocyte depleted type Worst prognosis
Features
Only 1% to 5% of classic cases
Pathological changes
Very little lymphoid tissue
Presence of R-S cells
Some contain a large number of R-S cells and may have diffuse fibrosis and necrosis.
Some cases are dominated by pleomorphic R-S cells, showing sarcoma-like appearance.
Some cases show diffuse fibrosis and few R-S cells
clinical manifestations
Performance
swollen lymph nodes
Like to occur in
Progressive enlargement of cervical or supraclavicular lymph nodes is the most common (60% to 80%), followed by axillary or inguinal, mediastinal and para-aortic lymph nodes
Features
Painless and progressive swelling of regional lymph nodes, involving the spleen, liver and bone marrow in the later stage
Enlarged lymph nodes can move, but if they adhere to each other and fuse into a mass, they will become inactive and feel cartilage-like when palpated.
Extralymphatic organ involvement
A small number of HL patients may infiltrate organ tissues or cause compression by enlarged deep lymph nodes, causing various corresponding symptoms.
systemic symptoms
Fever, night sweats, weight loss
1/6: Periodic fever (Pel-Ebstein fever)
Young women with itching (can be the only systemic symptom)
30%-40%: Unexplained persistent fever
Generally, they are older, more male, and often have retroperitoneal lymph node involvement.
other
Herpes zoster may occur in some cases
Lymph node pain after drinking alcohol
Unique to HL, but not all
installment
According to the extent of lymph node disease
Phase I
Only one site on one side of the diaphragm is involved
Phase II
One side of the diaphragm involves ≥2 sites
Stage III
Involvement of both sides of the diaphragm or spleen
Stage IV
One or more extranodal organs (bone marrow, lungs, liver, etc.)
Liver invasion: The liver is palpable under the ribs
Bone marrow invasion: Lymphoma cells appear in the bone marrow
According to systemic symptoms
Unexplained fever greater than 38°C
Night sweats
Weight loss of more than 10% within half a year
None of the three conditions were met, and they were group A (no systemic symptoms) One out of three is group B (with systemic symptoms)
diagnosis
Pathological diagnosis
Preferred bone marrow examination
The positivity rate is very low (only 3%)
Typical R-S cells have diagnostic value for HL
When diagnostic R-S cells are lacking, immunohistochemistry is required
CD30 is an activated lymphocyte antigen, and R-S cells in almost all CHL diseases are CD30 positive.
Tumor cells in 75%-85% of CHL cases express CD15
The tumor cell nuclei of 95% of CHL cases weakly express the B cell-specific activating factor protein PAX5/BSAP
treat
in principle
Comprehensive treatment of chemotherapy and radiotherapy is mainly used
Chemotherapy
The ABVD regimen has little impact on fertility and does not cause secondary tumors. Its efficacy is better than the MOPP regimen and is the preferred chemotherapy regimen for HL.
The MOPP regimen, whose main side effects are causing second tumors and infertility, has been replaced by the ABVD regimen.
radiotherapy
The lesions are irradiated on the diaphragm using a cloak style. The lesions are irradiated under the diaphragm using an inverted "Y" shape
plan
Nodular lymphocyte predominant type (Mostly stage IA)
Simple lymphadenectomy can be performed while waiting for observation or the involved field can be irradiated with 20-30Gy
Early (Phase I, II) treatment
Giving an appropriate amount of systemic chemotherapy tends to reduce the total dose of radiotherapy and narrow the scope of the radiation field. The ABVD regimen is used for chemotherapy.
Late stage (stage III, IV) treatment
If there is a large mass before chemotherapy or residual tumor after chemotherapy, combined with radiotherapy
For progression or early relapse during chemotherapy, salvage high-dose chemotherapy and hematopoietic stem cell transplantation should be considered
Treatment of relapsed and refractory Hodgkin lymphoma
Relapse after the first course of radiotherapy can be treated with conventional chemotherapy
If the patient is resistant to chemotherapy or cannot tolerate chemotherapy, radiotherapy may be feasible if the patient is re-staged into clinical stage I or II.
Second-line chemotherapy or high-dose chemotherapy and autologous hematopoietic stem cell transplantation are feasible for relapse after conventional chemotherapy.
Immunotherapy PD-1