What Is Diffuse Large B-cell Lymphoma?

Hodgkin's lymphoma, including classic Hodgkin's lymphoma and nodular lymphocytic predominant Hodgkin's lymphoma, is now considered a tumor of B-cell origin.

Wang Manju

(Deputy Chief Physician)

Department of Hematology, Peking University First Hospital

B-cell lymphoma is a solid tumor in which B cells develop. Including Hodgkin's lymphoma and non-Hodgkin's lymphoma. There are many types of Hodgkin's lymphoma, classic Hodgkin's lymphoma and nodular lymphocyte predominant Hodgkin's lymphoma, which are now considered to be B-cell-derived tumors. Diffuse large B-cell lymphoma, follicular lymphoma, mucosa-associated lymphoid tissue lymphoma (MALT), small lymphocytic lymphoma / chronic lymphocytic leukemia, mantle cell lymphoma (MCL) 5 types of B-cell non-Hodgkin Lymphoma is the most common, accounting for 3/4 of non-Hodgkin's lymphoma. The prognosis and treatment of B-cell lymphoma depends on the specific type and stage of the lymphoma.

Western Medicine Name: B-cell lymphoma

Main cause: Etiology unknown, immune deficiency, environmental factors
Contagious: Non-contagious

B-cell lymphoma disease classification

B B-cell lymphoma B-cell Hodgkin's lymphoma classification

Hodgkin's lymphoma, including classic Hodgkin's lymphoma and nodular lymphocytic predominant Hodgkin's lymphoma, is now considered a tumor of B-cell origin.

B B-cell lymphoma B-cell non-Hodgkin's lymphoma classification

B-cell non-Hodgkin's lymphoma 2008 WHO classification:

Precursor lymphoma

1. B lymphoblastic leukemia / lymphoma, not a special type

2.B lymphoblastic leukemia / lymphoma with recurrent genetic abnormalities

B lymphoblastic leukemia / lymphoma with t (9:22) (q34; q11.2); BCR / ABL

B lymphoblastic leukemia / lymphoma with t (v; 11q23); MLL rearranged

B lymphoblastic leukemia / lymphoma with t (v; 11q23); MLL rearranged (ETV6-RUNX1), B lymphoblastic leukemia / lymphoma with hyperdiploid

B lymphoblastic leukemia / lymphoma with hypodiploid

B lymphoblastic leukemia / lymphoma with t (5; 14) (q31; q32) (IL3-IGH)

B lymphoblastic leukemia / lymphoma with t (1; 19) (q23; p13.3); E2A-PBX1; TCF3 / PBX1)

Mature B-cell tumor

1. Chronic lymphocytic leukemia / small lymphocytic lymphoma

2.B-prelymphocytic leukemia

Splenic marginal lymphoma

4.Hair cell leukemia

5, splenic lymphoma / leukemia, can not be classified

6. Lymphoid plasma cell lymphoma

7, heavy chain disease

8. Plasma cell myeloma / plasma tumor

9. B-cell lymphoma at the edge of extranodal mucosa-associated lymphoid tissue (MALT lymphoma)

10.Primary skin follicular central lymphoma

Follicular lymphoma

-Gastrointestinal follicular lymphoma

-Follicular lymphoma in children

-"In situ" follicular lymphoma

B-cell lymphoma with inner edge of the node

Mantle cell lymphoma

14. Diffuse large B-cell lymphoma

-Diffuse large B-cell lymphoma, non-specific type

T-cell / histiocytic large B-cell lymphoma

Elderly EBV-positive diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma associated with chronic inflammation

-Empyema related lymphoma

-Chronic osteomyelitis-associated lymphoma

-Implant-associated lymphoma

Primary central nervous diffuse large B-cell lymphoma

-Lymphoma-like granuloma

Primary mediastinal (thymus) large B-cell lymphoma

-Intravascular large B-cell lymphoma

-Primary large skin B-cell lymphoma, leg type

-Plasmablastic lymphoma

-Primary leaky lymphoma

-ALK-positive diffuse large B-cell lymphoma

-Large B-cell lymphoma of HHV8-positive multicenter Castleman disease

15, Burkitt's lymphoma

16.Unclassifiable B-cell lymphoma between diffuse large B-cell lymphoma and Burkitt lymphoma

17.Unclassifiable B-cell lymphoma between diffuse large B-cell lymphoma and classic Hodgkin lymphoma

The following are five common B-cell NHLs that account for 3/4 of non-Hodgkin's lymphoma:

Diffuse large B-cell lymphoma

Follicular lymphoma

3. Mucosa-associated lymphoid tissue lymphoma (MALT)

4. Small lymphocytic lymphoma / chronic lymphocytic leukemia

5. Mantle cell lymphoma (MCL) ^[1-2]

B-cell lymphoma disease prognosis

According to different clinical behavior, B-cell lymphoma is divided into indolent lymphoma and invasive lymphoma. Indolent lymphoma usually develops slowly and can keep the disease stable and long-term survival for many years, but it cannot be cured. Invasive lymphoma usually requires a more intense treatment, but there is a possibility of cure. The prognosis and treatment of B-cell lymphoma depends on the specific type and stage of the lymphoma.

Shipp et al. Proposed the NHL International Prognostic Index (IPI) in 1993, which divided the NHL prognosis into four categories: low-risk, low-medium-risk, high-medium-risk, and high-risk.The estimated 5-year overall survival rates are 73%, 51%, and 43%, respectively. And 26%. Patients older than 60 years, staging in stage III or IV, more than 1 extranodal lesion, need bed rest or life to take care of others, and elevated serum LDH are 5 IPI with poor prognosis. NHL can be judged according to the number of IPI patients have Prognosis. ^[3]

B Monographs on B-cell lymphoma

B Diffuse large B-cell lymphoma

Diffuse large B cell lymphoma (DLBCL), DLBCL is the most common NHL, accounting for about 30% to 40% of all adult NHL, and the incidence is higher in China. DLBCL has significant heterogeneity in morphology, biological behavior and clinical. The 2008 WHO classification further divided it into three categories: non-specific (NOS), special subtypes and independent diseases.

Typical immunomarkers: tumor cells are CD45 positive, whole B cell markers (CD19, CD20, CD22), CD79a positive, cell membrane and / or cytoplasmic immunoglobulin (IgM> IgG> IgA) positive, immunoglobulin light chain restriction Sexual expression (- / + or + / -).

1. 1 DLBCL, NOS

This is a group of DLBCL that cannot be classified into a special subtype or independent disease. The vast majority of DLBCL belong to this group. According to tumor cell morphology, it can be divided into three kinds of common variants: central mother cell (CB), immunoblast (IB), and anaplastic and some rare variants (myxoid stroma, fibrillar matrix, pseudodaisy formation, shuttle Shape cells or signet ring cells, etc.).

According to gene expression profiling (GEP) analysis, DLBCL can be divided into two molecular subgroups: germinal center B cell (GCB) -like and activated B cell (ABC) -like. Among them, GCB-like accounts for 45% to 50%, but in China, GCB-like DLBCL accounts for only 20% to 30% of cases. Many studies have shown that the prognosis of GCB-like subgroups is better than that of ABC-like subtypes, and various morphological variants cannot reliably predict molecular subgroups.

Because GEP typing is not universally available at present, WHO classification recommends that DLBCL be divided into two subtypes based on the immunophenotype: (1) GCB-like: CD10 +, Bcl-6 +/-, MUM1 +/-, or CD10-, Bcl-6 +, MUM1 + /-; (2) Non-GCB-like: CD10-, Bcl-6 + /-, MUM1 + or CD10-, Bcl-6-, MUM1 + /-. Among them, the prognosis of GCB-like subgroups is better than that of non-GCB-like subgroups. The relationship between immunohistochemical clusters and molecular clusters roughly overlaps, but there are some differences.

The WHO classification also lists CD5 + DLBCL immune subgroups, but generally does not express CD23, cyclin D1, and is different from B small lymphocytic lymphoma and mantle cell lymphoma. This subgroup accounts for about 10% of all DLBCL cases. Most of them are primary DLBCL in non-GCB-like subgroups, and the prognosis is poor.

1.2 DLBCL subtype

1. 2. 1 T cell / histiocyte rich large B cell lymphoma (THRLBCL)

It accounts for less than 10% of all DLBCL. Tumors mainly involve lymph nodes. Tumor cells are always scattered in a large number of reactive T lymphocytes (CD3 +, CD45RO +) and tissue cells of varying numbers (CD68 +). At 10% or EBV +, THRLBCL should not be diagnosed.

1. 2. 2 Primary diffuse large B cell lymphoma of CNS (CNS DLBCL)

It refers to all LBCLs that originate in the brain or eyes, excluding LBCLs that occur in the dura mater, blood vessels, and secondary and immunodeficiency. Most tumor cells resemble CB, growing along the perivascular space and invading the brain parenchyma. The tumor cells show CD10 + (10% -20%), Bcl-6 + (60% -80%), and MUM1 + (90%), suggesting that most From non-GCB cells, the prognosis is poor.

1. 2. 3 primary cutaneous DLBCL, leg type

Occurs in the calf of elderly women. The tumor diffusely infiltrates the skin with a single CB and IB, but it is not epidermal. The tumor can often spread outside the skin. GEP and immunohistochemistry show that the tumor cells are ABC-like DLBCL, and the prognosis is poor. The 5-year survival rate is about 50%.

1. 2. 4 EBV positive diffuse large B cell lymphoma of the elderly

New classification classifies this type as a tentative type, an EBV-positive clonal large B-cell proliferative disease> 50 years old (median age 71 years), without immunodeficiency or history of previously existing lymphoma, diagnosis Other EBV-related diseases and lymphomas need to be excluded from time to time. About 2/3 of the cases occur outside the nodule, the tumor cells are large or pleomorphic, and may have the characteristics of IB or plasmablasts (PB). Tumors often have map-like necrosis, and the immunophenotype is usually CD10-, Bcl-6- , MUM1 +, LMP1 +, EBER +. The clinical course is rapid, the prognosis is poor, and the median survival time is about 2 years.

1.3 Independent diseases of DLBCL

1. 3. 1 primary mediastinal (thymic) large B cell lymphoma, PMBL

PMBL originates from thymic medullary B cells and is prevalent in young women. The clinical manifestation is a large mass in the anterior mediastinum. Tumors often spread to the kidney, adrenal gland, liver, CNS, and ovary. The tumor cells are large, rich in cytoplasm, transparent or lightly stained. The tumor cells are often surrounded by collagen fibers, and the immunophenotype is often CD30 + /-(weak and uneven), CD3 +, MAL +, MUM1 +, Ig-. Tumors respond better to intense chemotherapy and radiation therapy.

1. 3. 2 intravascular large B cell lymphoma (IVLBCL)

IVLBCL occurs in elderly men. It most often involves skin and CNS. It often invades the kidneys, lungs, adrenals, gastrointestinal tract, and soft tissues, and rarely involves lymph nodes. The tumor is composed of large cells (CB and IB), which are mainly located in the middle and small blood vessels of various organs, usually without obvious mass. The 2008 WHO classification describes Asian-type IVLBCL. Tumors affect the sinusoids of the liver, spleen, and bone marrow, with hepatosplenomegaly, hemophagocytic syndrome, and multiple organ failure. Tumor cells showed CD10-and MUM1 + /-. The patient progressed rapidly, responded poorly to treatment, and had a poor prognosis.

1. 3. 3 Large B-cell lymphoma with chronic inflammation (DLBCL associated with chronic inflammation)

Tumors occur on the basis of long-term chronic inflammation (empyema, osteomyelitis, metal implants, or skin ulcers) and EBV infection, which transforms, proliferates, escapes the body's immune surveillance system, and eventually progresses to DLBCL. Tumors are more common in elderly men. Tumor cells have CB and IB morphology, often with large necrosis and pro-vascular growth, and CD20-, CD138 +, and MUM1 + if there is significant plasma cell differentiation. EBV LMP1 +, EBER +, genetically abnormal expression of IF I27 gene. The tumor is aggressive, and the 5-year survival rate of empyema-associated lymphoma is only 25% to 30%.

1. 3. 4 lymphomatoid granulomatoid (LYG)

LYG is a vascular center and vascular destructive lymphoproliferative disease composed of EBV-positive B cells with a mixed number of reactive T cells. Tumors are more common in adult men, and the vast majority (> 90%) of patients have lung involvement. According to the number of EBV-positive B cells and polymorphic background components, LYS is divided into three levels, level 1: less atypical large cells, more inflammatory components, and focal necrosis, EBV + cells <5 cells / HPF; level 2: SARS There are more large-type large cells, less inflammatory components, and more common necrosis. 5-20 EBV + cells / HPF; Level 3: Atypical large cells, with insignificant inflammatory components, often large necrosis, EBV + cells> 20 / HPF, often up to hundreds. Ig gene rearrangement exists in grade 3 and some grade 2 LYGs. Early LYG was responded to INF2b treatment, and the prognosis was poor when it progressed to grade 3 (EBV + DLBCL), but recently, strong chemotherapy with melphalan has a certain effect.

1. 3. 5 ALK positive large B cell lymphoma (ALK + LBCL)

Tumors are common in middle-aged men and mainly involve lymph nodes and mediastinum. The tumor cells are large and simple, IB-like and PB-like, and often grow along the lymph nodes in the lymph nodes. Tumor cells express ALK, and the positive response is localized in the cytoplasm, granular. The typical immune phenotypes of DLBCL with ALK expression are CD45 +, EMA +, VS38c +, CD4 +, CD57 +, ALK +, all B marker negative (CD20-), CD138 +, MUM1 +, cIg + (IgA> IgG), CD30-, Genetically, t (2; 17) exists. The tumor progressed rapidly, was not sensitive to the treatment with Merlot, and the prognosis was poor. The median survival time of patients with stage to IV was only 11 months.

1.3.6 Plasmablastic lymphoma (PBL)

Tumors are more common in middle-aged and older men. Most patients have a history of immunodeficiency caused by HIV or other causes. Tumors are most often located in the mouth, but can also be located in other locations outside the nodule. Tumor cells have plasmablast (PB) morphology, CD20-, CD138 +, MUM1 +, c Ig + (mostly IgG), EBER +, but LMP1-. Oral mucosal PBL is usually CD56-. If CD56 is expressed, it may be suspected to be plasma cell myeloma. The prognosis of PBL is poor, and most patients die within 1 year after diagnosis.

1. 3. 7 large B cell lymphoma arising in HHV8-associated multicentric Castlemen disease

This is a multicenter Castleman disease (MCD) based on the addition of HHV8 infection, leading to the clonal proliferation of large B cells expressing IgM and PB morphological characteristics. Patients are often accompanied by HIV infection, clinically HHV8 MCD background, often involving lymph nodes and spleen, and may be associated with Kaposi sarcoma. Tumor cells express HHV8 latent nuclear antigen 1 (LANA1), c IgM +, +, CD20 + /-, CD79-, CD138-, and EBER +. The disease is highly malignant with a median survival time of only a few months.

1. 3. 8 primary effusion lymphoma (PEL)

PEL is a large B-cell lymphoma with tumor cells and no obvious mass in the exudate of the thoracic cavity, pericardial cavity, and peritoneal cavity. Tumors are associated with HHV8 infection. Most patients with AIDS who have HIV infection have monoclonal antibodies. Sexual EBV infection. Tumors occur in young men. Obviously abnormal IB and PB, tumor cells CD20-, CD79-, Ig-, CD138 +, EMA +, LANA1 +, EBER +, LMP1-were observed after centrifugation of the exudate. The prognosis of PEL is extremely poor, with a median survival time of only 6 months. It is now recognized that an extracorporeal lymphoma with a morphology and immunophenotype similar to PEL, which mainly affects the gastrointestinal tract, skin, CNS, lung or lymph nodes, is called extracorporeal PEL.

B-cell lymphoma follicular lymphoma

Follicular lymphoma (FL), according to the number of central blasts (CB) of each high-power field (HPF) in tumorous follicles 0 to 5, 6 to 15 and> 15 divided into 1, 2 And level 3. Because both grades 1 and 2 migrate to each other and clinical behavior is inert, the 2008 WHO classification merges them together as FL 1 to 2 while grade 3 is still based on the presence of central cells in the CB in tumor follicles. (CC) is divided into FL 3A (with CC) and FL3B (without CC). In the FL 1 ~ 2 level, the FL 3 area should be diagnosed separately, and the proportion of each level should be estimated. The presence of diffuse large B-cell areas in grade 3 FL should be diagnosed as: (1) diffuse large B-cell lymphoma (-%), (2) FL 3A or 3B (-%). When FL grade 3 or diffuse large cell areas appear, they should be treated as highly aggressive DLBCL.

The 2008 WHO classification also lists several variants of FL: (1) Pediatric FL: Occurs in men under 20 years of age, often involving cervical lymph nodes and oropharyngeal rings, and localized lesions. Tumorous follicles vary in size and shape, often large swollen follicles, and the mantle area can be retained. The tumor cells are mainly CB, Bcl2-and no t (14; 18), but Ig gene rearrangement has excellent prognosis; (2) Primary intestinal FL: occurs in the duodenum and appears as multiple small Polyps, most patients are clinical stage or E, the morphology, immunophenotype and genetic characteristics are similar to the lymph node FL, the prognosis is excellent, long-term survival even without treatment; (3) follicular tumor formation / "FL (intrafollicular neoplasia /" in situ "follicular lymphoma): When there are one or more follicles in normal lymph nodes or other lymphoid tissues, it is called" in situ "when Bcl-2 overexpresses CC and CB. FL, these patients may have FL in other parts at the same time, or one after another, but some patients have no evidence of FL after long-term follow-up. "In situ" FL must be diagnosed based on Bcl-2 immunohistochemical staining. The significance of this is not clear, but clinical examination should be performed to determine whether FL is present elsewhere. Follow-up is needed for patients without FL.

Typical immunophenotype: Tumor cells express cell membrane immunoglobulins (IgM +/- IgD, IgG, IgA), whole B cell markers (CD19, CD20, CD22), CD79a, CD10, BCL6, and do not express CD5, CD23, cyclin D1 . Most cases of FL express BCL2 (skin FL is generally BCL2-negative), which helps to distinguish it from reactive lymphoid follicle hyperplasia. The network formed by the proliferation of follicular dendritic cells in tumorous follicles can be displayed by staining with markers such as CD21, CD23, and CD35.

B-cell lymphoma Primary skin follicular central lymphoma

Primary cutaneous follicle centre lymphoma (PCFCT), a tumor that originates from mature B cells in the germinal center, is more common in middle-aged and elderly people, with a male-to-female ratio of 115: 1. Clinical manifestations are solitary or localized plaques, nodules or tumors in the upper trunk (especially the head and chest and back). The tumor is composed of medium to large CCs and varying numbers of CBs, showing a follicular and / or diffuse growth pattern, infiltrating the blood vessels and skin attachments without involving the epidermis. The immune phenotype is similar to that of lymph nodes FL, but Bcl-2 and Ig expression is usually negative, and genetically, there is no t (14; 18). PCFCT has an excellent prognosis, with a 5-year survival rate> 95%.

B-cell lymphoma extranodal mucosa-associated lymphoid tissue marginal zone lymphoma

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). The 2008 WHO classification provides a more precise description of the etiology, pre-tumor lesions, and genetics of MALT lymphoma. In terms of etiology, Helicobacter pylori infection is closely related to gastric MALT lymphoma; Chlamydia psittaci, Campylobacter jejuni, and Borrelia burgdorferi are associated with ocular appendage MALT lymphoma, immunoproliferative small bowel disease (IPSID), and cutaneous MALT lymphoma, respectively. Tumor-related; autoimmune diseases such as SjÖgren syndrome and Hashimoto thyroiditis are associated with MALT lymphoma of the salivary gland and thyroid, respectively. Genetic abnormalities known to be associated with MALT lymphoma include t (11; 18), t (14; 18), t (3; 14), and t (1; 14), of which t (11; 18) is mainly found in the lungs And gastrointestinal MALT lymphoma, t (14; 18) is mainly found in ocular appendages and salivary gland MALT lymphoma, and t (3; 14) is mainly found in thyroid, ocular appendages, and skin MALT lymphoma. In addition, +3 and +18 are often present, but these changes lack specificity.

Early gastric MALT lymphoma and IPSID are treated with antibiotics, and the tumor can be resolved or even completely cured, but if t (11; 18) is present, gastric MALT lymphoma is not treated with anti-helicobacter pylori, and chemotherapy is required, and t ( 11; 18) Gastric MALT lymphomas generally do not undergo diffuse large B-cell lymphoma transformation.

B-cell lymphoma chronic lymphocytic leukemia

Chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL). The 2008 WHO classification sets the diagnostic criteria for CLL as timely and exhaustive in extramedullary tissues, with a CLL phenotype in peripheral blood. (CD5 + CD23 +) monoclonal lymphocytes 5 × 109 / L. If the number of oligoclonal cells with CLL phenotype <5 × 109 / L appears in the blood of healthy people, it is called monoclonal B2cell lymphocytosis (MBL), which requires no special treatment in clinical practice, but requires Pay attention to follow-up. The diagnostic criteria for SLL are CLL morphology and immunophenotype in extramedullary tissue (usually lymph nodes) without leukemia.

Typical immunomarkers: Tumor cells express cell membrane IgM or IgM + IgD, whole B cell markers (CD19, CD20, CD22), CD79a, CD5, CD23, CD43, CD11c (weak), and do not express CD10, cyclin D1.

Studies have shown that only 40% to 50% of CLL's IgH V are not mutated, and 50% to 60% of CLL's IgH V have undergone somatic hypermutation. Unmutated CLL often expresses ZAP70 and CD38, and it is associated with poor prognosis. Mutated CLL mostly does not express ZAP70 and CD38. Therefore, immunohistochemical detection of ZAP70 and CD38 can indirectly reflect the IgH V mutation status of CLL and help to predict prognosis.

B-cell lymphoma mantle cell lymphoma

Mantle cell lymphoma (MCL). The 2008 WHO mentions the presence of "in situ" MCL that only affects the inner mantle region. In the morphological variants, "blastoid" and "pleomorphic" are listed as invasive variants of MCL; "small cells" and "marginal-like" are listed as MCL Other variants. The 2008 WHO also describes a Cyclin D1 and t (11; 14) negative, but other characteristics of Cyclin D1 negative MCL that are indistinguishable from usual MCL. These cases are highly expressed in Cyclin D2 or Cyclin D3, and some cases have t (2; 12 ), That is, the Cyclin D2 gene on chromosome 12 is fused with the kappa light chain gene on chromosome 2.

The 2008 WHO classification describes changes in the cell cycle and DNA damage repair pathways in MCL, and proposes the molecular mechanism of MCL occurrence, development and progression. When T (11; 14) chromosomal translocation occurs in unstimulated primary B lymphocytes, it can evolve into early MCL, followed by abnormal genetics of ATM and CHK2, which leads to increased genetic instability and develops into typical MCL.Some of these cases MCL tumor cell proliferation activity can also be increased due to the deletion or mutation of genes such as p16 / CDK4 / Rb and ARF / Mdm2 / p53, and progress to mother cell-like MCL.

The poor prognosis of MCL is related to high mitotic numbers (> 10 37.5 / 15 HPF,> 50mm2), high Ki267 index (> 40% or> 60%), blastoblast-like / polymorphic deformation, and +12. Genetic changes, complex karyotype, TP53 mutation / overexpression / loss, + 3q, -9q, and clinical lymphadenopathy with significant peripheral blood involvement.

B-cell lymphoma hairy cell leukemia

Hairy cell leukemia (HCL) and its related diseases, HCL is now thought to start from activated late-stage memory B cells. HCL tumor cells are small to medium large, rich in cytoplasm, lightly stained, clear cell borders, and many elongated cytoplasmic protrusions can be seen under the electron microscope. Tumor cells show a positive response to tartrate acid phosphatase (TRAP) .In addition to expressing CD19, CD20, and CD22 all-B antigens, the immunophenotype can also express CD103, CD123, DBA. 44, FMC7, and annexin A1 (Annexin). AnnexinA1 is only expressed in HCL, but not in any other B-cell lymphoma.

Splenic B cell lymphoma / leukemia, unclassifiable.

The 2008 WHO classification classified some small B-cell lymphomas of the spleen that do not yet have sufficient evidence to indicate an independent disease. They are tentatively classified as splenic B2cell lymphoma / leukemia (unclassifiable). Two tumors in this group of tumors are defined and described, one is splenic diffuse red pulp small B cell lymphoma, which diffusely infiltrates the spleen red pulp (including myelin and myelin). Sinus) is composed of small but single B cells, and tumors can also affect the sinusoids and peripheral blood of the bone marrow. The tumor cells had short villous processes, and the immunophenotypes were CD20 +, DBA. 44 +, IgG + / IgD-, while CD25, CD103, CD123, annexinA1, CD10, and CD23 were negative. After combining clinical, morphological, and immunophenotypic features, except CLL, PLL, SMZL, HCL, and LPL, it can be diagnosed as spleen red pulp diffuse small B-cell lymphoma. The other is hairy cell leukemia variant (HCLv), which has the characteristics of tumor cells in typical HCL and prolymphocytic leukemia (PLL), and the immunophenotype has certain characteristics of typical HCL, such as DBA 44+, FMC7 + and CD103 +, but CD25, annexinA1 and TRAP were negative. It is reported that the incidence of HCL2v in Asians is higher than that of typical HCL, and it responds poorly to conventional treatment regimens of HCL.

B-cell lymphoma

Lymphoplasmacytic lymphoma (LPL). LPL can only affect lymph nodes, but monoclonal IgM can be detected in the serum of many patients. When patients with LPL have bone marrow involvement and IgM monoclonal disease, they are called WaldenstrÊm macroglobulin. (WM), which is an important variant of LPL; Second, it was previously thought that up to 50% of LPL existed t (9; 14), which is actually very rare, and some cases (especially WM) often exist in -6q, but no Specificity; Third, heavy chain disease (HCD) is a type of HCD with a secreted truncated heavy chain but lacking a light chain binding site, usually accompanied by a morphology consistent with LPL.

B-cell lymphoma plasma cell tumor

Plasma cell neoplasms, real plasma cell neoplasms are tumors composed of terminal B cells that secrete monoclonal Ig (M protein), that is, plasma cells, including unidentified monoclonal gamma disease (MGUS), plasma Cell myeloma, plasma cell tumor, and immunoglobulin deposition disease. In 2001, heavy chain disease was classified as a plasma cell tumor, but the 2008 WHO classification listed HCD separately.This is because HCD and LPL (including WM) and plasma Cell tumors can also secrete Ig, but tumors are not only composed of plasma cells, but are composed of lymphocytes and plasma cells.

The 2008 WHO classification proposed that myeloma should be classified into symptomatic bone marrow based on serum and urine M protein, bone marrow clonal plasma cells or plasma cell tumors, and related organ or tissue damage (hypercalcemia, renal insufficiency, anemia, and bone lesions). Tumor and asymptomatic myeloma, the most important criterion of the former is the manifestation of terminal organ damage. Clinically, serum 2 microglobulin and albumin levels can be divided into 3 phases: 2 microglobulin <3.5mg / L, albumin> 3.5 g / dL in phase ; 2 microglobulin <3.5 mg / in phase L, albumin <3.5 g / dL or 2 microglobulin 3.5 to 5.5 mg / L regardless of albumin level; phase III 2 microglobulin> 5.5 mg / L. The median survival of the three groups was 62 months, 44 months, and 29 months. The prognosis of plasma cell myeloma can be predicted by cyclinD and translocation. The prognosis of D1 (11q13) or D3 (6p21) group is good, and the prognosis of D2 (4p16) or D1 + D2 group is poor. In addition, cytogenetics such as -13 or aneuploid, t (4; 14) or t (4; 16) or t (14; 20), -17p13, and low diploid plasma cell myeloma have a poor prognosis, Plasma cell myeloma of superdiploid t (11; 14) or t (6; 14) has a good prognosis.

B-cell lymphoma lymph node marginal zone lymphoma

Nodal marginal zone lymphoma. The 2008 WHO classification describes a tentative type of immunophenotype similar to that of adult NMZL-paediatric nodal marginal zone lymphoma (NMZL) in children. Tumors are more common in men ( The ratio of male to female ratio is 20: 1). Lymph nodes in the head and neck are usually asymptomatic, and 90% of the patients are stage . Histologically similar to adult NMZL, but often with germinal center progressive transformation, the outer edge of the follicle is ruptured and infiltrated by tumor cells. Children with NMZL have a good prognosis, can survive long-term after treatment, and rarely relapse.

B-cell lymphoma Burkitt's lymphoma

Burkitt lymphoma (BL). The 2008 WHO classification has a stricter definition of BL. Tumors mainly involve extranodules or manifest as acute leukemia. The tumor cells are single, medium in size, the tumor doubling time is very short, and the proliferative activity is very high, Ki267 + (~ 100%); immunophenotype shows CD20 +, CD10 +, Bcl-6 +, Bcl-2-, sIgM +; genetic There are t (8; 14), t (2; 8), or t (8; 22). BL is a highly invasive tumor, but it can be cured. The cure rate of early patients with intense combination chemotherapy can reach 90%, and the advanced patients can reach 60% to 80%.

Typical immunomarkers: tumor cells express membrane IgM and whole B cell antigens (CD19, CD20, CD22) CD10, BCL6, CD38, CD77, CD43, usually BCL2-, TdT-, almost 100% of cells are Ki-67 positive

B B-cell lymphoma

Can not be classified, with DLBCL and BL intermediate features (B cell lymphoma, unclassifiable, with features intermediate between diffuse large B cell lymphoma and Burkitt lymphoma), this is a morphological and genetic feature between DLBCL and BL, with The intermediate features of the two make it difficult to clearly classify them as any type of B-cell lymphoma. The 2008 WHO classification will be referred to as borderline disease, also known as grey zone lymphoma (GZL). The disease mainly occurs in adults and can affect lymph nodes and many areas outside the node. Tumor cells are medium to large; immunophenotypes show CD20 +, CD10 +, Bcl-6 +, Bcl-2 + /-, Ki267 + (50% to 100%); there are complex karyotype changes in genetics, often at the same time Chromosomal translocation involving MYC and BCL-2 genes. The tumor invasion is strong, and the patient's survival time is short.

B B-cell lymphoma

Cannot be classified, with DLBCL and classic Hodgkin lymphoma (CHL) intermediate features (B cell lymphoma, unclassifiable, with features between diffuse large B cell lymphoma and classical Hodgkin lymphoma) tumor clinically, morphologically and / or immunologically Type has the intermediate characteristics of DLBCL (especially PMBL) and CHL, but cannot be classified into any type. Tumors are more common in young men aged 20 to 40 years, and most of them are large masses in the anterior mediastinum. The tumor is composed of pleomorphic tumor cells fused into slices.The pleomorphic cells are similar to pit cells and H cells in HL.Some areas in the lesion are like CHL, others are like DLBCL2, and the interstitial is diffuse or focal fibers. The inflammatory background is usually not obvious, and necrosis is more common. Immunophenotype shows CD20 +, CD30 +, CD79 + /-, CD15 + /-, Bcl-6 + /-, CD10-, PAX5 +, OCT2 +, BOB. 1 +; genetically present + 2p and + 9q, GEP Analysis showed a close relationship between tumors and CHL and PMBL. Clinically, tumors are more aggressive and have a worse prognosis than CHL or PMBL. ^[3]