Adrenal Lymphoma
Adrenal lymphoma refers to involvement of one or both adrenal glands by a cancer of the lymphatic system. Secondary adrenal involvement by systemic lymphoma is much more common than true primary adrenal lymphoma, which is rare. Most cases are non-Hodgkin lymphoma, particularly diffuse large B-cell lymphoma. Adrenal lymphoma often presents with bilateral adrenal enlargement, sometimes accompanied by adrenal insufficiency, and is more common in older adults and in patients with immunosuppression. Imaging—particularly CT, MRI, and PET/CT—and tissue diagnosis are central to evaluation.
What is it?
The adrenal glands are two small triangular organs that sit on top of the kidneys. They produce several important hormones, including cortisol, which helps the body respond to stress and regulates metabolism, blood pressure, and immune function; aldosterone, which regulates sodium, potassium, and blood pressure; and adrenaline and noradrenaline, which help the body respond to acute stress.
Adrenal lymphoma refers to involvement of one or both adrenal glands by a cancer of the lymphatic system. Adrenal lymphoma is generally divided into two categories. Secondary adrenal involvement occurs when systemic lymphoma involves the adrenal glands along with other organs or lymph nodes and is by far the more common scenario.
Primary adrenal lymphoma is defined as lymphoma that is largely confined to one or both adrenal glands, with little or no involvement elsewhere at the time of diagnosis. Primary adrenal lymphoma is rare and most often occurs in older adults. It is reported more often in men and may occur in patients with immunosuppression, including people with HIV, transplant recipients, or patients receiving immunosuppressive medications.
The great majority of adrenal lymphomas are non-Hodgkin lymphomas, and the most common subtype is diffuse large B-cell lymphoma. Other subtypes can involve the adrenal glands less commonly, including some T-cell lymphomas, follicular lymphoma, and other rare aggressive lymphomas. Hodgkin lymphoma involving the adrenal glands is uncommon.
Bilateral adrenal involvement is a characteristic feature of primary adrenal lymphoma and is present in many patients at diagnosis.
Symptoms vary widely. Many patients present with nonspecific systemic features such as fatigue, unintentional weight loss, fevers, drenching night sweats—the classic “B symptoms” of lymphoma—and loss of appetite. Others develop back or flank pain, upper abdominal discomfort, or a palpable abdominal mass when tumors become very large.
A particularly important presentation is adrenal insufficiency, which can occur when both adrenal glands are extensively involved by lymphoma. Symptoms may include severe fatigue, weakness, dizziness, salt craving, low blood pressure, nausea, vomiting, weight loss, hyperpigmentation of the skin, low sodium, and high potassium. Severe adrenal insufficiency can cause adrenal crisis with shock.
Some patients are identified during staging or follow-up imaging performed for known systemic lymphoma, while others are diagnosed during the evaluation of unexplained symptoms.
Diagnosis combines clinical assessment, blood tests, imaging, and tissue confirmation. Blood tests may include a complete blood count, peripheral blood smear, comprehensive metabolic panel—particularly sodium, potassium, and glucose—LDH, morning cortisol, ACTH, HIV testing, hepatitis B and C testing, and other specialized studies based on the clinical situation.
Cosyntropin, or ACTH stimulation testing, may be used to assess adrenal function when adrenal insufficiency is suspected.
Imaging plays a central role. CT of the abdomen with intravenous contrast is commonly used and may show enlarged, often bilateral adrenal masses. The glands may retain part of their normal shape early in the disease and become more mass-like as involvement progresses.
Masses are often relatively homogeneous, although larger lesions may contain areas of hemorrhage or necrosis. Calcification is uncommon before treatment.
MRI with contrast provides additional characterization and may help distinguish lymphoma from other adrenal abnormalities. PET/CT is widely used for staging and treatment-response assessment in many lymphoma subtypes and can identify additional sites of disease.
Image-guided biopsy of the adrenal gland—usually a core biopsy performed under CT or ultrasound guidance—is often needed to establish the definitive diagnosis and lymphoma subtype, particularly when primary adrenal lymphoma is suspected.
Pheochromocytoma, a tumor that can produce adrenaline-like hormones, must be reasonably excluded before adrenal biopsy because biopsy of a pheochromocytoma can trigger a dangerous release of hormones.
Bone marrow biopsy may be performed in selected patients when PET/CT does not provide sufficient information or when identifying marrow involvement would affect staging or treatment decisions.
Important to Know
Treatment of adrenal lymphoma is driven by the specific lymphoma subtype, stage, presence or absence of adrenal insufficiency, and the patient’s overall health.
Care is best coordinated by hematologists and oncologists with lymphoma expertise, working with endocrinologists for adrenal insufficiency, infectious disease specialists for associated infections or immunosuppression, interventional radiologists, and, when relevant, surgeons and palliative care providers.
For aggressive B-cell lymphomas such as diffuse large B-cell lymphoma—the most common subtype involving the adrenal glands—the treatment backbone commonly includes chemoimmunotherapy combining rituximab with chemotherapy. The precise regimen is individualized based on the lymphoma subtype, disease burden, molecular features, patient age, and overall health.
Because adrenal involvement can be associated with an increased risk of central nervous system relapse in diffuse large B-cell lymphoma, the oncology team may perform additional risk assessment and consider CNS-directed evaluation or prophylaxis in selected patients. The benefit and preferred approach to prophylaxis remain uncertain and are individualized.
Other lymphoma subtypes have their own subtype-specific regimens. Targeted therapies, immune-based treatments such as bispecific antibodies and CAR T-cell therapy, stem cell transplantation, and clinical trials may be considered in selected patients, particularly when disease has relapsed or has not responded to initial treatment.
Adrenal insufficiency requires prompt attention. Patients diagnosed with adrenal insufficiency caused by lymphoma need hormone replacement with glucocorticoids and, when indicated, mineralocorticoids.
Treatment of the underlying lymphoma may improve adrenal function in some patients, but recovery is not guaranteed, and some patients require long-term hormone replacement after successful lymphoma treatment.
Patients receive education about stress dosing during illness, injury, or surgery; medical alert identification; and emergency glucocorticoid injection kits.
Management of associated conditions is also important. Patients with HIV, chronic hepatitis B or C, or other immunocompromising conditions require coordinated care with infectious disease or hepatology specialists. This includes treatment of the associated condition and measures to reduce complications such as hepatitis B reactivation during immunosuppressive therapy, which may require preventive antiviral medication.
Patients with prior transplants or those receiving immunosuppressive medications for other conditions require careful adjustment of their overall treatment plans.
Tumor lysis syndrome—a metabolic complication that can occur when rapidly growing lymphomas respond to treatment—requires preventive measures and close monitoring at the start of therapy.
Supportive and palliative care may play important roles throughout the course of disease. Pain management, nutritional support, mental health support, transfusion support, treatment of infections, and family-centered care planning may all be needed. Palliative care can be provided alongside active cancer treatment to help manage symptoms and support quality of life.
Surgical adrenalectomy is rarely the primary treatment for adrenal lymphoma because systemic therapy is the main treatment for most patients. Surgery is generally reserved for specific circumstances, such as persistent diagnostic uncertainty after less invasive approaches or rare individualized treatment situations.
Prognosis depends on the lymphoma subtype, stage, response to treatment, patient age and overall health, and associated conditions such as HIV or transplant status. Primary adrenal lymphoma has historically been associated with an unfavorable prognosis, but outcomes vary considerably, and modern systemic treatments have improved outcomes for some patients.
Imaging and laboratory findings are interpreted alongside the patient’s symptoms, examination, pathology results, and broader clinical context rather than in isolation.
Patients with adrenal lymphoma benefit from clear communication about the treatment plan, reasons for recommended therapies, warning signs that require urgent evaluation, and long-term follow-up.
Red-flag symptoms include severe weakness, dizziness or fainting, low blood pressure or signs of shock, rapid heart rate, cool or clammy skin, severe abdominal or back pain, high fever with chills, persistent vomiting, confusion, low blood sugar, or signs of severe infection.
These symptoms warrant immediate emergency evaluation because they may indicate adrenal crisis, severe infection, or another serious complication.