Clinical Manifestations of Non-Hodgkin Lymphoma: Recognizing the Diverse Symptoms and Systemic Impact
Non-Hodgkin lymphoma (NHL) is a highly heterogeneous group of blood cancers originating from lymphocytes, and its clinical presentation varies significantly among individuals. Because NHL can affect multiple organ systems and present with both localized and systemic symptoms, early recognition of signs is crucial for timely diagnosis and treatment. Unlike some cancers that follow a predictable pattern, NHL often mimics other conditions, making it a diagnostic challenge without proper evaluation.
Skin-Related Symptoms and Dermatological Involvement
Skin manifestations are prominent in certain subtypes of non-Hodgkin lymphoma, particularly cutaneous T-cell lymphomas such as mycosis fungoides. Patients may experience persistent pruritus (itching), which occurs in approximately 13% to 53% of cases. This symptom can precede diagnosis by months or even years, serving as an early but often overlooked warning sign.
Characteristic skin lesions include erythematous patches, papules, nodules, ulcers, and oozing sores. Secondary infections—such as herpes zoster—are common due to compromised immune function caused by the malignancy itself or immunosuppressive therapies. These infected lesions tend to be chronic and resistant to standard treatments, contributing to prolonged discomfort and increasing the risk of systemic complications, including recurrent fevers.
B-Systemic Symptoms: Unexplained Weight Loss and Night Sweats
Many patients with NHL develop B-symptoms—systemic indicators of advanced disease that include unexplained weight loss, drenching night sweats, and persistent fatigue. These symptoms result from tumor-induced metabolic changes and cytokine release, reflecting the body's ongoing struggle against cancerous cell proliferation.
Weight loss is typically defined as a reduction of more than 10% of body weight within six months without intentional dieting. Similarly, night sweats often soak through clothing and bedding, disrupting sleep and diminishing quality of life. The presence of B-symptoms not only affects patient well-being but also plays a role in staging the disease and guiding treatment intensity.
Localized Lymph Node Enlargement and Extranodal Spread
One of the most recognizable features of NHL is painless lymphadenopathy—enlarged lymph nodes in areas such as the neck, armpits, or groin. While these swellings are usually non-tender, they can compress nearby structures depending on their location, leading to symptoms like limb swelling, respiratory difficulty, or gastrointestinal obstruction.
Importantly, NHL frequently involves extranodal sites beyond the lymphatic system. Commonly affected organs include the gastrointestinal tract, bone marrow, skin, and nasal cavity. Gastrointestinal involvement may mimic irritable bowel syndrome or inflammatory bowel disease, presenting with abdominal pain, nausea, or even life-threatening perforation or obstruction.
Nasal and Sinonasal Lymphomas: A Distinct Subtype
In particular, natural killer/T-cell lymphoma (NKTCL), a subtype prevalent in parts of Asia and Latin America, often originates in the nasal cavity. Patients may report recurrent nosebleeds, nasal congestion, facial pressure, or sinus-like symptoms that resist conventional therapy. As the tumor progresses, it can erode surrounding tissues, causing facial swelling, dental pain, impaired hearing, and difficulties with swallowing or speech.
This aggressive form of NHL underscores the importance of considering lymphoma in patients with chronic rhinosinusitis unresponsive to antibiotics or surgery, especially when accompanied by systemic symptoms.
Abdominal Involvement and Organomegaly
Abdominal manifestations of non-Hodgkin lymphoma are clinically significant and commonly involve mesenteric or retroperitoneal lymph node enlargement. These internal masses may lead to vague or severe abdominal pain, early satiety, bloating, and in some cases, intestinal blockage requiring urgent intervention.
Hepatosplenomegaly—enlargement of the liver and spleen—is observed in a substantial number of NHL cases. While often asymptomatic initially, progressive organ involvement can result in abdominal fullness, discomfort, and abnormal liver function tests. Imaging studies such as CT scans or PET-CT are essential for detecting these internal changes, especially when physical examination findings are subtle.
Fever and Diagnostic Challenges
Fever is one of the most common systemic presentations of NHL, typically occurring in cycles and lacking a clear infectious source. Known as "fever of unknown origin" (FUO), this symptom often persists despite antibiotic therapy, prompting further investigation into underlying malignancies.
Because clinical signs alone cannot confirm lymphoma, definitive diagnosis relies on histopathological analysis—usually through lymph node biopsy or bone marrow aspiration. Immunohistochemistry and molecular testing help classify the specific subtype, which directly influences prognosis and therapeutic decisions.
Early awareness of the diverse clinical expressions of non-Hodgkin lymphoma—from skin rashes and night sweats to gastrointestinal disturbances and unexplained fevers—can accelerate diagnosis and improve outcomes. Given its variable nature, a high index of suspicion is vital, especially in patients with persistent, atypical symptoms that defy routine explanation.