DLBCL is a Non Hodgkin Lymphoma (NHL)—a very aggressive neoplasm unless diagnosed and treated timely (survival is less than 1 year without cure). This is B-Lymphocyte (B-cell) fast growing lymphoma (unlike Follicular lymphoma), affecting lymph nodes though cancerous cells, which might be found outside the lymphatic system. DLBCL accounts for a third of all NHLs; this is the most common cancer in the western world. This illness is characterized by enlarged nodes, which are initially painless as in the majority of all lymphoma cases; this type of blood cancer has a very close affiliation with genetic issues, Epstein-Barr virus ( EBV) and immune compromised conditions (congenital and acquired: HIV, AIDS).

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Image: “Micrograph of a diffuse large B cell lymphoma, abbreviated DLBCL. Lymph node FNA specimen. Field stain.” by Nephron. License: CC BY-SA 3.0 DE

Image: “Micrograph of a diffuse large B cell lymphoma, abbreviated DLBCL. Lymph node FNA specimen. Field stain.” by Nephron. License: CC BY-SA 3.0 DE


WHO/REAL Classification

  • DLBCL, not otherwise specified (NOS)
  • T-cell/Histiocyte rich large B-cell lymphoma
  • Primary DLBCL of the central nervous system (CNS)
  • Primary cutaneous DLBCL, leg type
  • Epstein-Barr virus (EBV)-positive DLBCL of the elderly
  • Germinal center B-cell (GCB)-DLBCL
  • Activated B-cell (ABC)-DLBCL­­

Basing on the DNA microarray, DLBCL can be divided into subgroups with germinal center B-cell–like (GCB), activated B-cell–like (ABC), or type 3 gene expression profiles. There is a significantly better survival in GCB group than in the ABC group. The type 3 group is heterogeneous and not well determined, but has a bad outcome similar to the ABC group.

Also, DLBCL can be divided into 2 molecularly distinct populations (cured and fatal/refractory) this method is very expensive, so a simpler, more widely available method to subclassify DLBCL into molecularly distinct and prognostically makeable groups employing immunohistochemistry would have wide usage and practical application in everyday clinical practice.


The most probable triggering factor of DLBCL has not been determined precisely yet.

Nevertheless, possible risk factors for the malignant transformation of the blood cells are

  • obesity
  • geriatric age
  • genetic factor(family history of hematopoietic malignancy)
  • immunosuppression
  • chronic inflammation
  • environmental factors(living close to industrial areas)
  • increased recreational sun exposure
  • long-term exposure to exposure chemicals(, herbicides, insecticides, and oxidative dye)
  • autoimmune diseases
  • organ transplantation
  • infections caused by Epstein-Barr virus (EBV), Kaposi sarcoma-associated human herpes virus 8 (HHV 8), Helicobacter pylori, Chlamydia psittaci, and hepatitis C virus (HCV)


DLBCL is the most common type of lymphomas in the US, moreover there is an increase in the number of the cases of DLBCL observed from year to year in both genders, races and ages apart from the young one. Men are slightly more susceptible to this illness rather than women. The incidence of DLBCL is lower in black Americans and other minority groups, though the most advanced cases of the disease are diagnosed mid the youngest black population of the USA.


Ann Arbor staging system

Stage I: Involvement of a single lymph node or of a single extranodal organ or site (IE)

Stage II: Involvement of 2 or more lymph node regions on the same side of the diaphragm, or localized involvement of an extranodal site or organ (IIE) and one or more lymph node regions on the same side of the diaphragm

Stage III: Involvement of lymph node regions on both sides of the diaphragm, which may also be accompanied by localized involvement of an extranodal organ or site (IIIE) or spleen (IIIS) or both (IIISE)

Stage VI: Diffuse or disseminated involvement of one or more distant extranodal organs with or without associated lymph node involvement

Reference: https://www.biooncology.com/pathways/b-cell/dlbcl/staging-dlbcl.html

Clinical Presentation

The manifestation of DLBCL is very similar to follicular lymphoma or any other types of the immune system cancer, most of the case are accompanied by enlarged and swollen lymph nodes, though the symptoms may differ within the localization of the malignant process. Moreover, over 40% of the patients have extranodal manifestation of the disease, namely, skin, gastrointestinal tract, central nervous system(CNS), respiratory system (lungs), genitourinary tract(prostate), or the bones.

  • Rapidly enlarged causing no pain lymph nodes.
  • So-called B-symptoms (fever, night sweats, and weight loss).
  • Itchiness
  • Pelvic lymphadenopathy leads to pedal edema due to the blockage of the lymph outflow
  • Breathlessness
  • Fatigue

Physical Examination

First of all the targeted for the cancerous cells tissue is lymphoreticuloendothelial (lymph nodes, spleen, liver, and bone marrow), thus cervical, axillary, and inguinal nodes may be enlarged, also, there can be splenomegaly respectively. As the extranodal symptoms may vary depending on the localization, there might be some symptoms of organ malfunction due to the obstruction with malignant growth (affected CNS, liver, kidneys).


Laboratory studies

  • Complete blood cell CBC (assessment of bone marrow and immunological function and diagnostic of anemia, thrombocytopenia, and/or leukopenia)
  • Flow cytometry (peripheral blood examination for circulating tumor cells)
  • Biochemical test of the level of Calcium in the blood ( (paraneoplastic syndrome) such as hypercalcemia) should be detected in case of lymphoma.
  • Comprehensive metabolic panel:
    • serum electrolytes
    • lactic dehydrogenase (LDH)
    • renal function
    • hepatic function
    • serum β2 microglobulin (B-cell lymphoma) testing
  • Histological examination of the biomaterial obtained from excisional biopsy of the affected nodes.(Diffused spread of abnormally enlarged cells, there are equal number of small and large cells, with cleaved or indented nucleus and coarse chromatin in them)
    Figure: Diffuse large B-cell lymphoma. Hematoxylin and eosin stain of a lymph node biopsy sample showing a mixture of large and small cells. The architecture of the node is lost, with a diffuse pattern of involvement.
  • Bilateral iliac crest bone marrow biopsies (staging) determines the rate of the bone marrow involvement.
  • Lumbar puncture in advanced cases(cytologic and chemical analysis of the cerebrospinal fluid)

Imaging studies

  • CT of neck, chest, abdomen, and pelvis in order to distinguish the advance of the disease.
    Figure: Patient with diffuse large B-cell lymphoma with extranodal involvement. This computed tomography (CT) scan shows an enlarged spleen and liver as a result of Lymphomatous involvement.http://img.medscapestatic.com/pi/meds/ckb/40/36540tn.jpg
    Figure: Patient with diffuse large B-cell lymphoma with extranodal involvement (same patient as in the previous image). This patient has an enlarged spleen and liver as a result of lymphomatous involvement. Extensive retroperitoneal lymphadenopathy is also present.
  • Bone imaging is compulsory if there is unexplained pain in bones and / or elevated alkaline phosphatase levels in the blood.

Differential Diagnosis

  • Benign inoculation lymphoreticulosis
  • Follic Sarcoidosis
  • Tuberculosisular lymphoma
  • Lymphomatoid granulomatosis
  • Lymphoblastic lymphoma
  • Malignant anaplastic (Ki 1+) lymphoma
  • Mantle cell lymphoma
  • Mediastinal lymphoma
  • Lymphomatoid granulomatosis


Since DLBCL may turn into a fulminant form, the treatment has to commence immediately.

  • Chemotherapy, monoclonal antibody rituximab (Rituxan), radiation therapy may lead to remission.
  • R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) 12 cycle
  • Chemotherapy coupled with stem cell transplantation in case of relapse of the disease.
  • Cell transplantation (autologous stem cell transplant) own cells are used.
  • Donor cell transplantation (allogeneic stem cell transplant).
  • Regular checkup.


There are different types of marginal zone lymphomas.

  • Extranodal marginal zone B-cell lymphoma (mucosa-associated lymphoid tissue (MALT) lymphoma)
  • Nodal marginal zone B-cell lymphoma
  • Splenic marginal zone B-cell lymphoma

Extranodal marginal zone B-cell lymphomas have a more or less benign outcome than the other types. Almost 90 out of 100 people with this type of marginal zone lymphoma (90%) will survive for 5 years or more after they are diagnosed.

B cell lymphomas regarded to marginal zone lymphomas that are slow growing.

Survival for high grade lymphomas:

Stage 1: Survival for 5 years or more after diagnosis around 80 out of 100 people (around 80%)

Stage 2: Survival for 5 years or more after diagnosis 75 out of 100 people (75%)

Stage 3: Survival for 5 years or more after they are diagnosed, more than 50 out of 100 people (more than 50%)

Stage 4: Survival for 5 years or more after their diagnosis, around 65 out of 100 people (around 65%)

High grade (aggressive) lymphomas frequently require more intensive treatment than the low grade types. Fortunately they often respond well to treatment as the number of people cured completely is relatively high. The most common type of high grade lymphoma is diffuse large B cell lymphoma.

Survival statistics are available for each stage of diffuse B cell lymphoma in one area of England. This is for people diagnosed between 2004 and 2011:

Stage 1: Survival for 5 years or more after they are diagnosed, 65 out of 100 people (around 65%)

Stage 2: Survival for 5 years or more after diagnosis, around 70 out of 100 people (around 70%)

Stage 3: Survival for 5 years or more after diagnosis, over 50 out of 100 people (over 50%)

Stage 4: Survival for 5 years or more after their diagnosis, almost 50 out of 100 people (almost 50%)

Review Questions

The correct answers can be found below the references.

1. A 67 years old patient, former lumber worker, with 32 years’ experience, complains on enlarges neck nodes and feeling very tired after insignificant work load and bone pain even in rest, which he cannot affiliate with the weather changes or physical activities. His body temperature is 38,9°, he is sweaty and weak. CBC reveals low erythrocyte and platelet count. Serum examination indicated enhanced level of Calcium in the blood. The biopsy of the neck node reflected such a picture: there is an equal number of big and small cells mixture which have coarse chromatin in cleaved nucleus. What is the most probable diagnosis?

  1. Follicular lymphoma.
  2. Tuberculosis.
  3. Sarcoidosis.
  4. Diffuse large B-cells lymphoma.
  5. Mantle cell lymphoma

2. Diffuse large B-cells lymphoma is:

  1. Fast growing ruthless if there is no timely treatment neoplasm, triggered by carcenous B-lymphocytes, NHL.
  2. Slow growing regardless treatment neoplasm, triggered by carcerous lymphocytes, NHL.
  3. Moderately growing on the background of proper chemotherapy neoplasm, triggered by carcerous B-lymphocytes NHL.
  4. Fast growing regardless treatment neoplasm, triggered by T-lymphocytes.
  5. None of above.

3. What are the most informative methods of diagnostics of DLBCL?

  1. CBC, Flow cytometry, calcium in blood serum, LDH, serum β2 microglobulin (B-cell lymphoma) testing biopsy of the affected node or the organ tissue, CT.
  2. CBC, Potassium and folate in the blood serum, serum β2 microglobulin (B-cell lymphoma) testing CT, kidney tests, X-ray.
  3. CBC, Calcium in the blood serum, CT (bone scan), ECG, urine examination, serum β2 microglobulin (B-cell lymphoma) testing.
  4. CBC, cholesterol, serum β2 microglobulin (B-cell lymphoma) testing, X-ray, ECG, Flow cytometry, potassium in the blood serum.
  5. None of above.
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