History

The clinical manifestations of diffuse large B-cell lymphoma (DLBCL) are diverse and depend on the site of disease involvement. These tumors have a rapid growth rate and present as masses, causing symptoms when they infiltrate tissues or obstruct organs. Although lymphadenopathy may initially be painless, pain in an enlarged lymph node or affected organ may be noted if the lymphomatous mass enlarges rapidly.

As with other types of non-Hodgkin lymphoma (NHL), DLBCL can manifest with B symptoms: fever higher than 38°C, night sweats, and/or weight loss of more than 10% of body weight in the preceding 6 months. Generalized pruritus may also be present.

Other signs and symptoms can include the following:

Anorexia
Pedal edema - Caused by extensive pelvic lymphadenopathy
Fatigue
Chest discomfort or shortness of breath - Caused by mediastinal lymphadenopathy

Medical history should include inquiries about the following:

Duration/intensity of symptoms, with special attention to B symptoms
Neurological or gastrointestinal manifestations
History of environmental and/or infectious pathogens (eg, HIV, hepatitis B or C virus)
Exposure to certain viral organisms, which may affect treatment selection or outcome

Physical Examination

On physical examination, keep in mind that diffuse large B-cell lymphoma (DLBCL) appears most frequently in lymphoreticuloendothelial tissues, which include the lymph nodes, spleen, liver, and bone marrow. However, any extranodal site may be primarily or secondarily involved, including the central nervous system (CNS), lungs, gastrointestinal tract, genitourinary tract, and bones.

Involvement of sanctuary sites, including the CNS and testicles, occurs more commonly with the following disorders:

Burkitt and non-Burkitt lymphoma
HIV-associated lymphoma
Human T-cell leukemia virus (HTLV) type 1–associated lymphoma
Primary CNS lymphoma
Primary testicular diffuse large cell lymphoma

The following are common findings on physical examination in patients with DLBCL:

Lymphadenopathy - Ie, cervical, axillary, and inguinal
Splenomegaly
Low-grade fever
Pedal edema - Resulting from extensive pelvic lymphadenopathy

The clinical spectrum observed in lymphoma patients is diverse and is influenced by the subtype of lymphoma and its anatomical relationship with other organs and/or systems. Symptoms vary from painless lymph node enlargement to rapidly progressive lymphadenopathy and extranodal disease associated with end-organ damage (eg, superimposed infection, bone marrow, renal, hepatic or cardiac failure).

The clinical characteristics observed in lymphoma patients can be grouped in the following categories:

Structural dysfunction of anatomy such as, swelling, pain, organ obstruction, ulceration, or bleeding
Disruption of normal organ function as the result of extranodal involvement of liver, CNS, or kidney
Remote dysfunction of organ function (ie, paraneoplastic syndrome) such as hypercalcemia and B-symptoms (ie, night sweats, fever, itching, weight loss)

A complete physical examination should include evaluation of the following:

All lymph node chains
Cardiopulmonary system
Liver and spleen
Pelvis
Breasts
Testicles
Skin
Neurological aspects, to detect subtle signs of early CNS involvement or cord compression

Differential Diagnoses

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Media Gallery

Biopsy of a cervical lymph node showing infiltration with a population of large cells (B cells) consistent with diffuse large cell lymphoma.
Computed tomography (CT) scan of the abdomen showing mesenteric and retroperitoneal adenopathy in a patient with diffuse large cell lymphoma.
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.
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.
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.
This image depicts gallium scans performed as part of a staging workup for a patient with diffuse large B-cell lymphoma. The scans show extensive hepatosplenic and multiple sites of nodal involvement with a gallium-avid tumor.
Role of B-cell receptor signaling in promoting proliferation and survival of DLBCL. BCR is the main factor in B-cell biology, playing a key role in B-cell development, antigen-driven clonal selection, and humoral immunity. B-cell receptor signaling activates PI3K-mediated activation of the kinase AKT, which activates many downstream signaling pathways. All these downstream pathways are essential for the survival of B cells. PIP3 is generated as a result of BCR-dependent PI3K activation. BTK also hydrolyzes PIP2 into DAG and IP3. IP3 induces release of calcium stores from the endoplasmic reticulum. Ca and DAG activate PKC, which leads to activation of NF-k B pathyway. PI3K, phosphatidylinositide-3 kinase; AKT, protein kinase B; PTEN, phosphatase and tensin homolog; PIP2, phosphatidylinositol-4,5-bisphosphate; PIP3, phosphatidylinositol-4,5-trisphosphate; IKK, IkB kinase; mTOR, mammalian target of rapamycin; FoxO, Forkhead box transcription factors; GSK3b, glycogen synthase 3-beta; p21, inhibitor of cyclin-dependent kinases.

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Author

Shipra Gandhi, MBBS Resident Physician, Department of Internal Medicine, University of Buffalo, State University of New York School of Medicine and Biomedical Sciences

Shipra Gandhi, MBBS is a member of the following medical societies: American College of Physicians

Disclosure: Nothing to disclose.

Coauthor(s)

Andre M Kallab, MD Clinical Associate Professor of Oncology, Medical College of Georgia; Consulting Staff, Department of Oncology, Northeast Georgia Diagnostic Clinic

Andre M Kallab, MD is a member of the following medical societies: American College of Physicians, American Medical Association, American Society of Hematology

Disclosure: Nothing to disclose.

Francisco J Hernandez-Ilizaliturri, MD Professor of Medicine, Department of Medical Oncology, Associate Professor of Immunology, Department of Immunology, Chief, Lymphoma and Myeloma Section, Director, The Lymphoma Translational Research Program, Roswell Park Cancer Institute, University of Buffalo State University of New York School of Medicine and Biomedical Sciences

Francisco J Hernandez-Ilizaliturri, MD is a member of the following medical societies: American Association for Cancer Research, American Society of Hematology

Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Acknowledgements

Asher A Chanan-Khan, MD Assistant Professor, Department of Medicine, Division of Lymphoma and Bone Marrow Transplantation, Roswell Park Cancer Institute, State University of New York at Buffalo

Disclosure: Nothing to disclose.

Wendy Hu, MD Consulting Staff, Department of Hematology/Oncology and Bone Marrow Transplantation, Huntington Memorial Medical Center

Disclosure: Nothing to disclose.

Michael Paul Kosty, MD Associate Director, Associate Professor, Department of Internal Medicine, Divisions of Supportive Care Services and Hematology and Oncology, Ida M and Cecil H Green Cancer Center, Scripps Clinic

Disclosure: Nothing to disclose.

Clifford H Pemberton, MD Instructor in Medicine, Jefferson Medical College; Medical Director, Jefferson Hospice and Palliative Care Program; Consulting Staff, Department of Medicine, Division of Hematology/Oncology, Lankenau Hospital

Clifford H Pemberton, MD is a member of the following medical societies: American Academy of Hospice and Palliative Medicine, American College of Physicians, American Medical Association, American Society of Hematology, and Pennsylvania Medical Society

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment