Diffuse Large B Cell Lymphoma

DIFFUSE LARGE B CELL LYMPHOMA(DLBCL) 

• It is the most common form of NHL(Non-Hodgkin’s Lymphoma).It is a tumour of the mature B cells.
  • The most common variant of Non-Hodgkin’s Lymphoma in India is Diffuse Large B cell Lymphoma.
  • Diffuse Large B cell Lymphoma is also the most common variant of Non-Hodgkin’s Lymphoma in the United States.
• It is rapidly fatal if untreated.

IMMUNOPHENOTYPE

• They will demonstrate markers of mature B lymphocytes as well as germinal centre markers- CD 19- CD 20 – CD 10- BCL-6- slg- BCL-2 (see in 10% to 20% associated with t(14:18)).

CLINICAL FEATURES OF DIFFUSE LARGE B CELL LYMPHOMA

• Incidence of this lymphoma is more common in males(male-to-female disease incidence ratio of 1.3:1).
• DLBCL typically affects patients in their sixth decade, except for primary mediastinal DLBCL variant, which affects mostly females in their late 20s or early 30s.
• These tumors have a rapid growth rate and present as masses, causing symptoms when they infiltrate tissues or obstruct organs.
• Two thirds NHLS present with nontender nodal enlargement.
• Two thirds of NHLS arise at extranodal sites which are skin, stomach or brain.
• As with other types of non-Hodgkin lymphoma (NHL), diffuse large cell lymphomas can present with B-symptoms, including fever, drenching night sweats, and weight loss.
• Most common extranodal site for non – hodkin’s lymphoma is Stomach.
• 60-80% of intestinal lymphomas are B cell lymphomas, mostly diffuse large B cell type of Non Hodgkin’s lymphoma of the distal small intestine and especially in the ileo-cecal region
• Most common ocular lymphoma is B Cell Non Hodgkin’s Lymphoma.Most common Lymphoma of Thyroid are of Non-Hodgkin’s B Cell Type.The paraneoplastic hypercalcemia in lymphoma is due to ectopic production of 1,25 dihydroxyvitamin D.
  • B cell lymphoma, Burkit lymphoma, Non Hodgkin’s lymphoma, mantle cell lymphoma are common in orbit.
• 5 year survival rate of Diffuse large B cell lymphoma is 46%.

CYTOGENIC ABNORMALITIES AND ONCOGENE ASSOCIATED WITH DIFFUSE LARGE B CELL LYMPHOMA

• Cytogenic Abnormality associated with Diffuse Large B Cell Lymphoma is t(3;-)(q27;-)t(17;-)(p13;-).
• Oncogene associated with Large B Cell Lymphoma is BCL-6,p53.

• Disease                                           Cytogenetic Abnormality                Oncogene
• Mantle cell lymphoma                                t(11;14)(q13;q32)               BCL-1, IgH
• Follicular lymphoma                                  t(14;18)(q32;q21)                BCL-2, IgH
• Diffuse large cell lymphoma                       t(3;-)(q27;-)t(17;-)(p13;-)    BCL-6,p53
• Burkitt’s lymphoma,Burkitt’s leukemia        t(8;-)(q24;-)                        C-MYC
• CD30+ Anaplastic large cell lymphoma       t(2;5)(p23;q35)                    ALK
• Lymphoplasmacytoid lymphoma                t(9;14)(p13;q32)                  PAX5, IgH

CLASSIFICATION OF NHL
Working formulation in staging of non-hodgkins lymphoma is based on Morphology of Cells.:

• Low grade:Small lymphocytic,Follicular, predominantly small cleaved cell ,Follicular, mixed, small cleaved and large cell.
  • Follicular cell lymphoma falls under the low grade non-Hodgbkins lymphoma .
  •  Lymphomas with a follicular histological pattern have a longer survival than those of diffuse pattern.
    
• Intermediate grade:Follicular predominantly large cell ,Diffuse small cleaved cell,Diffuse mixed small and large cell,Diffuse large cell.High grade:Large cell immunoblastic,Lymphoblastic,Small non cleaved cell.
  • Diffuse small, mixed , as well as large cell Lymphoma falls in the Intermediate form of Non-Hodgkin’s Lymphoma.

The classification proposed by the International Lymphoma Study Group for non-Hodgkin’s lymphoma is known as REAL Classification(‘Revised European-American Classification of Lymphoid Neoplasms (REAL).)

• In addition to morphologic descriptions, this schema includes immunologic, cytogenetic, and molecular information to define distinct lymphoma entities
• WHO has now reviewed and updated the real classification:WHO Classification / Modified ‘REAL’ Classification..
• Currently, diffuse large B-cell lymphoma is designated under the REAL classification as classic diffuse large cell lymphoma of B-cell origin .

INTERNATIONAL PROGNOSTIC INDEX(IPI) FOR NHL:

• The IPI score system is calculated by the sum of the presence or absence of 5 variables :age ≥ 65 y, performance status ≥ 2, elevated lactate dehydrogenase (LDH), Ann Arbor stage III or IV, and ≥2 extranodal sites of disease.
• Based on the total score, DLBCL patients are assigned into 4 risk category groups (low, low-intermediate, high-intermediate, and high).

DIAGNOSIS

•  The diagnosis of diffuse large cell lymphoma is usually confirmed after positive findings are obtained from a lymph node biopsy specimen
• Distinction between a poorly differentiated carcinoma and a lymphoma can be made by immunoperoxidase staining of the tumour tissue with antibodies directed against Cytokeratin.
• Immunohistochemical stains is used for the diagnosis of lymphomas is CD45 (leucocyte common antigen).
• Routine CT scanning of the neck, chest, abdomen, and pelvis is the standard imaging study for patients with lymphoma.
• Gallium-67 (67 Ga) scans are valuable in the staging of diffuse large cell lymphomas.
• Currently the Ann Arbor staging system is the preferred staging system for DLBCL.
  • Stage I – Involvement of a single lymph node region (I) or localized involvement of a single extralymphatic organ or site (I E)
  • Stage II – Involvement of 2 or more lymph node regions on the same side of the diaphragm (II) or localized involvement of a single associated extralymphatic organ or site and its regional lymph nodes, with or without involvement of other lymph node regions on the same side of the diaphragm (II E)
  • Stage III – Involvement of lymph node regions on both sides of the diaphragm (III), which may also be accompanied by localized involvement of an associated extralymphatic organ or site (III E ), by involvement of the spleen (III s), or by both (III E+S)
  • Stage IV – Disseminated (multifocal) involvement of one or more extra lymphatic organs, with or without associated lymph node involvement, or isolated extralymphatic organ involvement with distant (nonregional) nodal involvement
  • A – No systemic symptoms present
  • B – Unexplained fever ≥ 38 o C; drenching night sweats; weight loss ≥ 10% body weight.

TREATMENT

• In general, the role of surgery in the treatment of diffuse large cell lymphomas is limited.
• Treatment of these tumors is primarily with cytotoxic agents, with or without radiation therapy.
• The treatment of diffuse large B-cell lymphoma (DLBCL) should include the use of rituximab- and anthracycline-based-multiagent chemotherapy.
• Rituximab is a targeted antibody against cell surface molecule CD-20.
  • It is used in :B-cell lymphomas: Low grade lymphomas, mantle cell lymphomas, relapsed aggressive B cell lymphomas, CLL;SLE and Rheumatoid Arthritis.

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