Non-Hodgkin Lymphoma (NHL) Clinical Presentation

Updated: Jun 22, 2023
  • Author: Sanjay Vinjamaram, MD, MPH; Chief Editor: Emmanuel C Besa, MD  more...
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The clinical manifestations of non-Hodgkin lymphoma (NHL) vary with such factors as the location of the lymphomatous process, the rate of tumor growth, and the function of the organ being compromised or displaced by the malignant process.

The Working Formulation classification groups the subtypes of NHL by clinical behavior—that is, low-grade, intermediate-grade, and high-grade. Because the Working Formulation is limited to classification based upon morphology, it cannot encompass the complex spectrum of NHL disease, excluding important subtypes such as mantle cell lymphoma or T cell/natural killer cell lymphomas. However, it continues to serve as a basis for understanding the clinical behavior of groups of NHLs.

Low-grade lymphomas

Peripheral adenopathy that is painless and slowly progressive is the most common clinical presentation in these patients. Spontaneous regression of enlarged lymph nodes can occur in low-grade lymphoma, potentially causing confusion with an infectious condition.

Primary extranodal involvement and B symptoms (ie, temperature >38°C, night sweats, weight loss >10% from baseline within 6 mo) are not common at presentation, but they are common in patients with advanced, malignant transformation (ie, evolution from a low-grade to an intermediate- or high-grade lymphoma) or end-stage disease.

Bone marrow is frequently involved and may be associated with cytopenia or cytopenias. [1] Fatigue and weakness are more common in patients with advanced-stage disease.

Intermediate- and high-grade lymphomas

These types of lymphomas cause a more varied clinical presentation. Most patients present with adenopathy. More than one third of patients present with extranodal involvement; the most common sites are the gastrointestinal (GI) tract (including the Waldeyer ring), skin, bone marrow, sinuses, genitourinary (GU) tract, thyroid, and central nervous system (CNS). B-symptoms are more common, occurring in approximately 30-40% of patients.

Lymphoblastic lymphoma, a high-grade lymphoma, often manifests with an anterior superior mediastinal mass, superior vena cava (SVC) syndrome, and leptomeningeal disease with cranial nerve palsies.

Patients with Burkitt lymphoma (occurring in the United States) often present with a large abdominal mass and symptoms of bowel obstruction. Obstructive hydronephrosis secondary to bulky retroperitoneal lymphadenopathy obstructing the ureters can also be observed in these patients.

Primary CNS lymphomas are high-grade neoplasms of B-cell origin. Most lymphomas originating in the CNS are large cell lymphomas or immunoblastomas, and they account for 1% of all intracranial neoplasms. These lymphomas are more commonly observed in patients who are immunodeficient because of conditions such as Wiskott-Aldrich syndrome, transplantation, or AIDS (see HIV-Associated Opportunistic Neoplasms-CNS Lymphoma for more information on this topic). [6]

Fernberg et al examined time trends in risk and risk determinants in posttransplant patients with lymphoma and found that posttransplant NHL risk decreased during the 2000s compared with the 1990s among patients who underwent nonkidney transplants. [15]


Physical Examination

Low-grade lymphomas may produce peripheral adenopathy, splenomegaly, and hepatomegaly. Splenomegaly is observed in approximately 40% of patients; the spleen is rarely the only involved site at presentation.

Intermediate- and high-grade lymphomas may produce the following physical examination findings:



Potential disease-related complications include the following:

  • Cytopenias (ie, neutropenia, anemia, thrombocytopenia) secondary to bone marrow infiltration; alternatively, autoimmune hemolytic anemia is observed in some types of NHL (eg, small lymphocytic lymphoma /chronic lymphocytic leukemia [SLL/CLL])

  • Bleeding secondary to thrombocytopenia, disseminated intravascular coagulation (DIC), or vascular invasion by the tumor

  • Infection secondary to leukopenia, especially neutropenia

  • Cardiac problems secondary to large pericardial effusion or arrhythmias secondary to cardiac metastases

  • Respiratory problems secondary to pleural effusion and/or parenchymal lesions

  • Superior vena cava (SVC) syndrome secondary to a large mediastinal tumor

  • Spinal cord compression secondary to vertebral metastases

  • Neurologic problems secondary to primary CNS lymphoma or lymphomatous meningitis

  • GI obstruction, perforation, and bleeding in a patient with GI lymphoma (may also be caused by chemotherapy)

  • Pain secondary to tumor invasion

  • Leukocytosis (lymphocytosis) in leukemic phase of disease