Diffuse Large B-Cell Lymphoma (DLBCL)

Diffuse large B-cell lymphoma (DLBCL) is an aggressive type of lymphoma that affects about 5.6 per 100,000 people every year.1 It is a fast-growing cancer that can have nodal and extranodal presentations, and it is the most common type of non-Hodgkin lymphoma identified in adults (up to 40% of cases).1-3 Cancer cells build up in the lymphatic tissue but can arise in any part of the body, particularly in the gastrointestinal tract.2,3 In extranodal disease, DLBCL most commonly arises in the gastrointestinal tract, skin, soft tissues, bone, and genitourinary tract, and it can advance to areas such as the bone marrow, pleura, peritoneum, liver, and central nervous system (CNS).4

Diffuse large B-cell lymphoma is often symptomatic.1 The clinical manifestations observed in patients vary according to the organs involved. However, it is typical to note a rapid growth of masses involving 1 or more lymph nodes and extranodal sites.2 These masses may compromise the functioning of different organs and lead the patient to experience different symptoms.5 

Typical Signs and Symptoms of DLBCL

Upon physical examination, doctors may detect cervical, axillary, and inguinal lymphadenopathy, which may be painless in the early phases, splenomegaly, and low-grade fever.6 Patients can also present with increased serum lactate dehydrogenase and beta-2-microglobulin levels.2

Typical signs and symptoms of DLBCL include6,7:

  • Pain in lymph nodes or organs, which may be enlarged
  • Pain in the chest and shortness of breath due to mediastinal lymphadenopathy
  • Bone pain
  • Generalized pruritus
  • Anorexia
  • Fatigue
  • Pedal edema due to pelvic lymphadenopathy

Other symptoms include gastrointestinal issues such as abdominal discomfort or pain, nausea with or without vomiting, diarrhea, and bleeding.8,9 The salivary glands, nasal sinuses, and eyes can also be affected depending on the pressure the lymphoma is causing to these structures.8 

Signs and symptoms deriving from CNS involvement include confusion, memory changes, seizures, weakness, and numbness. When DLBCL affects the bone marrow, patients present with a low blood count, which results in shortness of breath, unusual bleeding or bruising, and persistent infections.9 

B symptoms affect about one-third of patients with DLBCL and include fever >38 °C, night sweats that can soak through clothes, and unexplained weight loss of more than 10% of the patient’s body weight within the last 6 months.2,7 

A complete medical history should focus on: understanding the duration and intensity of the reported symptoms; if there is any neurological or gastrointestinal involvement; and if there is any history of contact with infectious pathogens such as hepatitis viruses or human immunodeficiency virus (HIV).5 

Signs and Symptoms Associated With DLBCL Variants

In the World Health Organization (WHO) classification of lymphomas, about 80% of DLBCL cases are classified as “not otherwise specified,” while the remaining 20% are classified as specific variants of the disease. These variants present with particular features and represent distinct clinicopathological presentations of DLBCL.10

Patients with primary mediastinal B-cell lymphoma may experience respiratory difficulties due to airway obstruction as a bulky anterior/superior mediastinal mass compresses the trachea. This mass can also cause a blockage of the superior vena cava, triggering superior vena cava syndrome with swelling of the arms and face.10-12 Patients with this DLBCL variant often present with cervical and supraclavicular lymphadenopathy, and about one-third present with B symptoms.10,12

In patients with T-cell/histiocyte-rich large B-cell lymphoma, B symptoms and hepatosplenomegaly are commonly observed. Patients with anaplastic lymphoma kinase (ALK)-positive large B-cell lymphoma commonly present with generalized lymphadenopathy. In patients with intravascular large B-cell lymphoma, manifestations of the CNS are commonly observed, along with hepatosplenomegaly and hemangioma of the skin.10

Read more about DLBCL types


1. Harris LJ, Patel K, Martin M. Novel therapies for relapsed or refractory diffuse large B-cell lymphoma. Int J Mol Sci. 2020;21(22):8553. doi:10.3390/ijms21228553

2. Li S, Young KH, Medeiros LJ. Diffuse large B-cell lymphoma. Pathology. 2018;50(1):74-87. doi:10.1016/j.pathol.2017.09.006

3. NCCN guidelines for patients: diffuse large B-cell lymphoma, 2020. National Comprehensive Cancer Network (NCCN). Accessed August 12, 2022.

4. Ollila TA, Olszewski AJ. Extranodal diffuse large B cell lymphoma: molecular features, prognosis, and risk of central nervous system recurrence. Curr Treat Options Oncol. 2018;19(8):38. doi:10.1007/s11864-018-0555-8

5. Gandhi S. Diffuse large B-cell lymphoma (DLBCL) clinical presentation. Medscape. Updated May 6, 2021. Accessed August 12, 2022.

6. Gandhi S. Diffuse large B-cell lymphoma (DLBCL): practice essentials. Medscape. Updated May 6, 2021. Accessed August 12, 2022.

7. Diffuse large B-cell lymphoma (DLBCL) symptoms and diagnosis. Blood Cancer UK. Accessed August 12, 2022.

8. Diffuse large B-cell lymphoma. Leukaemia Foundation. Updated June 20, 2020. Accessed August 12, 2022.

9. Diffuse large B cell lymphoma (DLBCL). Lymphoma Australia. Accessed August 12, 2022.

10. Sukswai N, Lyapichev K, Khoury JD, Medeiros LJ. Diffuse large B-cell lymphoma variants: an update. Pathology. 2020;52(1):53-67. doi:10.1016/j.pathol.2019.08.013

11. Types of B-cell lymphoma. American Cancer Society. Updated January 29, 2019. Accessed August 12, 2022.

12. Chen H, Pan T, He Y, et al. Primary mediastinal B-cell lymphoma: novel precision therapies and future directions. Front Oncol. 2021;11:654854. doi:10.3389/fonc.2021.654854

Reviewed by Kyle Habet, MD, on 8/31/2022.