Discovering a persistent, swollen lump, particularly a lymph node in the neck, armpit, or groin, can be a source of significant anxiety. The immediate fear for many is lymphoma or another type of cancer. After a medical evaluation and a biopsy, a patient might receive a pathology report with a confusing term: lymphoid hyperplasia. While this medical terminology can sound intimidating, it is crucial to understand what it means and what it does not. Lymphoid hyperplasia is not a disease itself, but rather a benign (non-cancerous) and appropriate overreaction of the immune system. It is a sign that your body’s defense network is working hard to fight off an infection or inflammation. Understanding this “great imitator” of lymphoma is essential for alleviating fear and focusing on the real task: finding and treating the underlying trigger.

Lymphoid hyperplasia is a benign condition characterized by a rapid increase in the number of normal, healthy lymphocytes, causing an enlargement of the lymphoid tissues where they live. To understand this, it is essential to first understand the lymphatic system.

The lymphatic system is a vital part of your body’s immune defense network. It is made up of the spleen, tonsils, adenoids, and hundreds of small, bean-shaped structures called lymph nodes that are located throughout your body. These lymph nodes act as command centers or military barracks for your immune cells, primarily the lymphocytes (B-cells and T-cells).

A helpful analogy is to think of a lymph node as a small military barracks located in a specific district of your body. The soldiers inside are the lymphocytes.

• Lymphoma is like a mutiny inside the barracks. A single “rogue soldier” (a cancer cell) begins to clone itself endlessly, producing a disorganized army of identical, dysfunctional soldiers that take over the barracks and can spread to other locations. The problem is a cancer of the soldiers themselves.
• Lymphoid Hyperplasia is completely different. In this case, the barracks and all the soldiers are healthy, normal, and loyal. But an “invader” (like a virus or bacteria) has been detected in the local district. In response, the central command sends an emergency signal to the local barracks to rapidly train and deploy troops. The barracks becomes overcrowded and bustling with many different types of well-trained soldiers (a “polyclonal” population), all working together to fight the real threat. The barracks swells in size due to this appropriate and intense activity.

The problem is not the barracks or the soldiers; it is the invasion they are fighting. This benign, reactive swelling is lymphoid hyperplasia.

In my experience, lymphoid hyperplasia is often mistaken for a malignancy when enlarged lymph nodes are first discovered, especially on imaging or routine exams.

The cause of lymphoid hyperplasia is always an underlying stimulus that activates the immune system and tells the lymphocytes to multiply. The body is essentially ramping up its defenses to deal with a perceived threat.

The most common categories of causes include:

• Infections: This is the most frequent cause. The lymphatic system is the body’s first line of defense against invading germs.
  • Viral Infections: Common viruses like Epstein-Barr virus (the cause of mononucleosis), cytomegalovirus (CMV), and even the common cold can cause reactive swelling of the lymph nodes in the neck. HIV is also a major cause of persistent generalized lymphadenopathy.
  • Bacterial Infections: A strep throat can cause the tonsils and neck lymph nodes to swell. An infection with the bacterium Helicobacter pylori is a very common cause of lymphoid hyperplasia in the stomach. Widespread infections like tuberculosis can also cause significant lymphoid hyperplasia.
• Autoimmune Diseases: In conditions like rheumatoid arthritis or lupus, the immune system is chronically over-stimulated, which can lead to persistent enlargement of the lymph nodes.
• Certain Medications: Some drugs, such as phenytoin (an anti-seizure medication), can cause a benign, reactive lymph node enlargement.
• Idiopathic: In some cases, particularly in children and young adults, a lymph node may be enlarged, and even after a biopsy, no specific cause is found. This is often presumed to be a reaction to a minor, unidentified infection that the body has already cleared.

In my experience, it can also result from persistent antigenic stimulation like chronic tonsillitis, autoimmune diseases, or even after vaccination.

A person develops lymphoid hyperplasia as a normal and healthy response of their immune system to one of the triggers listed above. It is not contagious, although the underlying infections that cause it (like mononucleosis or a cold) certainly can be. It is not an inherited condition. It is simply a sign that your immune system is working as intended.

In my experience, patients develop it when their immune system reacts vigorously to an infection or ongoing inflammation often unknowingly.

Lymphoid hyperplasia itself does not have symptoms. It is a microscopic finding on a biopsy or a physical finding on an exam. The signs and symptoms a person experiences are entirely due to the underlying condition that is causing the immune system to react.

• The Primary Sign: The physical sign is the enlargement of lymphoid tissue. This most often presents as lymphadenopathy, or swollen lymph nodes. These can be felt as lumps in the neck, armpits, or groin. The nodes may be tender if they have enlarged rapidly in response to an acute infection.
• Symptoms of the Underlying Cause:
  • If the hyperplasia is caused by mononucleosis, the person will have a sore throat, fever, and profound fatigue.
  • If it is caused by H. pylori in the stomach, the person may have symptoms of indigestion or stomach pain.
  • If it is part of an autoimmune disease, the person will have the symptoms of that specific condition, such as joint pain.

Clinically, I distinguish it from malignancy by noting the soft, mobile nature of the lymph nodes and lack of systemic features like weight loss or night sweats.

When a person has a persistently swollen lymph node without a clear cause, a doctor’s primary goal is to rule out lymphoma. The entire diagnostic process is geared toward confidently distinguishing between a benign reactive process and a malignant one.

1. Medical History and Physical Exam: A doctor will ask about recent illnesses, fevers, night sweats, or weight loss and will perform a thorough exam to check the size and texture of the lymph nodes and look for enlargement elsewhere (like the spleen).
2. Biopsy: If a lymph node remains enlarged for several weeks without a clear explanation, a biopsy is essential to determine the cause. An excisional biopsy, where the entire lymph node is surgically removed, is the preferred method as it allows the pathologist to examine the complete structure of the node.
3. Pathology Examination: This is the most critical step. A hematopathologist (a pathologist specializing in blood and lymph node diseases) will examine the tissue under a microscope. They look for several key features to differentiate hyperplasia from lymphoma:
   • Lymph Node Architecture: In benign hyperplasia, the overall structure and different zones of the lymph node are preserved. In lymphoma, the cancer cells often completely overrun and destroy the normal architecture.
   • Cell Population: In a reactive process, the lymph node is filled with a healthy, diverse mixture of different types of immune cells. This is called a polyclonal population. In most lymphomas, the node is taken over by a monotonous sheet of identical-looking cancer cells that are all clones of a single malignant cell. This is called a monoclonal population.
   • Specialized Tests: The pathologist will use advanced tests like immunohistochemistry and flow cytometry. These tests use antibodies to analyze the specific proteins on the lymphocyte surface to definitively confirm if the population is a benign polyclonal mix or a malignant monoclonal clone.

Once lymphoma has been definitively ruled out by the biopsy, the doctor’s focus shifts to finding the underlying cause of the benign reaction. This may involve blood tests for infections like EBV or HIV, or an endoscopy to test for H. pylori.

Clinically, I rely on history, physical exam, and sometimes ultrasound or CT to evaluate lymph node characteristics. Biopsy is used when cancer can’t be ruled out.

Benign reactive lymphoid hyperplasia itself requires absolutely no treatment. It is not a disease, but rather a sign that your immune system is functioning properly. Having a large number of healthy soldiers in the barracks is a good thing when there is a battle to be fought.

Treatment is still directed to the underlying cause that is triggering the immune response.

• If the cause is a bacterial infection (like strep throat or H. pylori), the treatment is a course of antibiotics.
• If the cause is a viral infection (like mononucleosis), the treatment is supportive care (rest, fluids), as the body’s immune system will clear the virus on its own.
• If the cause is an autoimmune disease, a rheumatologist will manage the underlying condition with specific immunosuppressive medications.

Once the underlying trigger is successfully treated and resolved, the stimulus for the immune system to be on high alert will disappear. The swollen lymph nodes will then gradually shrink back to their normal size over a period of weeks to months.

I typically adopt a watch-and-wait approach especially if the cause is clearly reactive and self-limiting, like a recent viral illness.

Discovering a persistent swollen lymph node can be a source of great fear, with the immediate concern often being lymphoma. While a biopsy is always necessary to be certain, it is reassuring to know that a very common outcome is a diagnosis of benign reactive lymphoid hyperplasia. This is not a diagnosis of cancer, but rather a confirmation that your immune system is healthy and is mounting a strong, appropriate response to an underlying infection or inflammation. Diagnosing lymphoid hyperplasia is good news. It allows you and your doctor to confidently shift focus away from the fear of cancer and toward the straightforward task of identifying and treating the underlying condition that triggered your body’s powerful and protective immune response in the first place.

1. The Merck Manual Professional Version. (2022). Lymphadenopathy. Retrieved from https://www.merckmanuals.com/professional/hematology-and-oncology/lymphadenopathies/lymphadenopathy
2. American Cancer Society. (2024). Non-Hodgkin Lymphoma. Retrieved from https://www.cancer.org/cancer/types/non-hodgkin-lymphoma.html
3. National Institutes of Health, MedlinePlus. (2023). Swollen lymph nodes. Retrieved from https://medlineplus.gov/ency/article/003097.htm