Non-Hodgkin’s lymphoma (also termed non-Hodgkin lymphoma, NHL) is a type of blood cancer that develops in the lymphatic system. In NHL, abnormal growth of white blood cells (lymphocytes) occurs, which can form tumors throughout the body. NHL grows and spreads at varying rates and can be indolent (grow and spread slowly) or aggressive (grow and spread rapidly).

Symptoms

The common symptoms of non-Hodgkin's lymphoma may include:

• Painless swelling in a lymph node, typically in the groin, armpit, or side of the neck.

• Abdominal pain or swelling, nausea, or vomiting.

• Chest pain, cough, or breathlessness.

• Persistent fatigue

• Fever without an infection.

• Night sweats

• Unexplained weight loss.

• Constant itchiness of the skin all over the body.

• Red or purple lumps or bumps under the skin.

Other symptoms, such as swollen tonsils, a mass in the abdomen, or skin rashes, depend on the location of where in the body the lymph glands are enlarged.

Diagnosis

NHL is diagnosed using various tests. The utilization of a test depends on several variables, including the type of lymphoma suspected, the patient's symptoms, age, and general health, as well as the outcomes of prior diagnostic procedures.

Medical history and physical examination

A patient’s complete medical history is elicited, including details about their symptoms, potential risk factors, and other medical disorders. During physical examination, lymph nodes and other affected areas of the body, including the spleen and liver are examined for swelling or any infections.

Blood tests

Blood tests including complete blood count (to rule out anemia, leukopenia, thrombocytopenia, pancytopenia, thrombocytosis, and lymphocytosis), serum chemistry tests (to rule out tumor lysis syndrome), and level of lactate dehydrogenase may be prescribed by the clinician to check for infections.

Histopathological examination

A biopsy followed by histopathological examination is preferred for the definitive diagnosis of NHL. If the size, texture, or location of a lymph node or the presence of additional symptoms strongly suggest lymphoma, an immediate biopsy may be required. There are various kinds of biopsies, such as:

• Incisional (removal of a small portion of a bigger tumor or node) or excisional (removal of the complete lymph node) biopsy.

• Needle biopsy techniques include fine needle aspiration biopsy and core needle biopsy.

• Bone marrow aspiration and biopsy: These procedures are frequently carried out following a lymphoma diagnosis to determine the spread of cancer to the bone marrow.

• Lumbar puncture (spinal tap): This test looks for lymphoma cells in the cerebrospinal fluid.

• Pleural or peritoneal fluid sampling: A hollow needle inserted through the skin into the chest or abdomen to extract pleural fluid (inside the chest) or peritoneal fluid (inside the abdomen).

Imaging modalities

Imaging studies may be carried out to assess potential causes of specific symptoms (such as enlarged lymph nodes in the chest, chest discomfort, or breathing difficulties) and to establish the stage of cancer. Following imaging tests may be used to diagnose NHL.

• Chest x-ray

• Computed tomography (CT) scan: A CT scan of the head, neck, chest, abdomen, and pelvis is frequently recommended because a CT scan produces a sequence of incredibly detailed images of areas inside the body.

• Magnetic resonance imaging (MRI) scan: Although MRI is less frequently utilized than CT scans for lymphoma, it is nevertheless highly helpful for examining the progression of cancer to the brain or spinal cord.

• Ultrasonography: Ultrasonography can be used to examine lymph nodes close to the surface of the skin or to scan the interior of the abdomen for enlarged lymph nodes or other organs like the liver and spleen.

• Positron emission tomography (PET) scan: Following a lymphoma diagnosis, a PET scan may be performed to check whether an enlarged lymph node contains lymphoma and to identify any other affected region in the body.

• Bone scan: A radioactive material called technetium is injected into a vein for bone imaging. A specialized camera can then detect the radiation after it has reached the damaged bone regions. A bone scan may reveal bone involvement and damage caused by lymphoma.

Management

Depending on the type and the stage of the NHL and the patient’s preferences and overall health, treatment options for people with NHL might include:

• Watchful waiting: Some persons with indolent lymphoma may not require immediate treatment if the lymphoma is not causing any symptoms. This is referred to as watchful waiting, watch-and-wait, or active surveillance. Doctors constantly monitor patients while they are undergoing watchful waiting using routine physical examinations, imaging studies, and laboratory tests. 

• Chemotherapy: Drugs are used in chemotherapy to destroy cancer cells, mainly by preventing them from proliferating, dividing, and producing new cells. It is the primary NHL treatment. A patient may take 1 drug at a time or a combination of drugs taken together, including:

1. Cyclophosphamide

2. Doxorubicin

3. Prednisone

4. Vincristine

• Radiation therapy: Radiation therapy uses high-energy X-rays, electrons, or protons to kill cancer cells. Radiation therapy for NHL is typically external-beam radiation therapy (delivered from a machine outside the body). Depending on the NHL subtype, it is typically given after or with chemotherapy. 

• Targeted therapy: Targeted therapy specifically targets the cancer-specific genes, proteins, or tissue environment that promotes the growth and survival of the disease. It comprises kinase inhibitors (Ibrutinib, Acalabrutinib, Zanubrutinib, Pirtobrutinib, and Copanlisib), immunomodulatory drugs (Lenalidomide, Tazemetostat, and Venetoclax), and nuclear export inhibitors (Selinexor). 

• Cellular immunotherapy and checkpoint inhibitors: Immunotherapy uses the body's immune system to fight cancer. Immunotherapy for NHL includes monoclonal antibodies (rituximab, brentuximab vedotin), chimeric antigen receptor (CAR) T-cell therapy, and checkpoint inhibitors (pembrolizumab). 

• Bone marrow/stem cell transplant: In this technique, hematopoietic stem cells which are found in bone marrow or peripheral blood cells, are used. It is also termed a stem cell transplant or hematopoietic stem cell transplant. It is considered an aggressive treatment for the NHL. Only those with recurrent or progressive NHL are often treated with it.

Moreover, the course of treatment varies depending on the stage and subtype of the NHL. A combination of these treatments may be used to achieve better outcomes.