Small lymphocytic lymphoma (SLL) is a type of non-Hodgkin lymphoma, a cancer that begins in the lymphatic system. This cancer specifically affects B-lymphocytes, or B-cells, which are white blood cells responsible for producing antibodies to fight infection. SLL is characterized by the uncontrolled growth and accumulation of these malignant B-cells, primarily within the lymph nodes and other lymphoid tissues. It is classified as an indolent or slow-growing lymphoma, meaning it often progresses gradually over many years.
Defining Small Lymphocytic Lymphoma
The cancerous B-cells in SLL are functionally impaired, which can lead to a compromised immune system and increased susceptibility to infections. SLL is considered a chronic condition, and it is most frequently diagnosed in older adults, often around 65 years of age.
The relationship between SLL and Chronic Lymphocytic Leukemia (CLL) is fundamental to understanding the disease. The World Health Organization classifies SLL and CLL as two manifestations of the same underlying biological cancer. Both conditions involve the same type of abnormal B-cell and share identical genetic and cellular characteristics.
The distinction between SLL and CLL is based primarily on where the cancerous cells are concentrated in the body. SLL is used when malignant B-cells are predominantly confined to the lymph nodes and lymphoid organs, such as the spleen. Conversely, CLL is applied when the abnormal cells are found mainly in the bloodstream and the bone marrow. SLL is diagnosed when the number of abnormal B-cells in the blood is less than 5,000 per microliter, while CLL is diagnosed when this count is 5,000 or more.
Despite this difference in location, the two conditions are treated similarly, and the prognosis is comparable. It is common for SLL cases to eventually involve the blood and transform into what is clinically managed as CLL. Many individuals live with SLL for a long period, often without the need for immediate therapeutic intervention.
Recognizing Signs and Symptoms
SLL is often discovered during a routine physical examination or through blood tests before any noticeable symptoms appear. Many people remain asymptomatic for a significant time after diagnosis. When symptoms do manifest, the most common physical sign is the painless enlargement of lymph nodes.
Swollen lymph nodes, resulting from the accumulation of malignant B-cells, are frequently observed in the neck, armpits, or groin area. Spleen enlargement is also possible, which can cause a feeling of fullness or discomfort in the upper left side of the abdomen. The presence of non-localized symptoms, often grouped as “B symptoms,” can indicate more active or advanced disease.
The B symptoms include unexplained fevers persisting for at least two weeks and drenching night sweats. Significant, unintentional weight loss, defined as more than 10% of total body weight over six months, is another systemic sign. These systemic signs, along with persistent fatigue not relieved by rest, are indicators that the disease may be progressing.
Diagnostic Procedures and Disease Staging
Diagnosis of SLL typically begins with a physical examination to check for enlarged lymph nodes and assess the patient’s overall health. Blood tests, such as a complete blood count (CBC), are routinely performed to count white blood cells, including lymphocytes. A peripheral blood smear is also examined to look at the size, shape, and appearance of the circulating cells, which offers initial clues.
The definitive diagnosis of SLL requires a lymph node biopsy, where a surgeon removes all or part of a swollen lymph node for laboratory analysis. Pathologists use specialized tests, like flow cytometry, to identify characteristic markers on the B-cells, such as CD5 and CD19, confirming the cancer type. Imaging studies, such as CT scans or PET scans, are used to determine the location and extent of the lymphadenopathy throughout the body.
To assess the full extent of the disease and its involvement of the bone marrow, a bone marrow aspiration and biopsy are frequently performed. These procedures collect samples from the hip bone to determine the percentage of abnormal cells present. Specialized genetic tests, such as Fluorescence In Situ Hybridization (FISH), detect specific chromosomal abnormalities or gene mutations, providing prognostic information that guides treatment decisions.
Once the diagnosis is confirmed, the disease is staged to determine its spread, which is crucial for treatment planning. SLL/CLL staging often relies on the simpler Rai or Binet systems, which are tailored to this specific condition, rather than the Ann Arbor system. Staging ranges from Stage 1, where cancer is confined to a single lymph node area, to Stage 4, where the disease has spread to organs outside the lymphatic system, such as the liver or lungs.
Current Treatment Approaches
The management of SLL is individualized, depending on the patient’s age, overall health, genetic markers, and disease stage. For many patients who are asymptomatic, the standard initial approach is “Watchful Waiting,” also known as active surveillance. Starting treatment immediately does not improve overall survival for asymptomatic patients and exposes them to unnecessary side effects.
During Watchful Waiting, the patient is closely monitored with regular physical examinations and blood tests to track progression. Active treatment is initiated only when the patient develops significant symptoms, such as B symptoms, massive enlargement of lymph nodes or spleen, or evidence of bone marrow failure.
The initial therapeutic strategy often involves chemoimmunotherapy, combining traditional chemotherapy agents (such as fludarabine and cyclophosphamide) with monoclonal antibodies (such as rituximab). Newer, highly effective options now include targeted therapies that interrupt specific pathways within the cancer cells.
Targeted therapies include Bruton Tyrosine Kinase (BTK) inhibitors, such as ibrutinib or acalabrutinib, which block signals that promote B-cell growth. Another class is BCL-2 inhibitors, such as venetoclax, which restore the cell’s ability to undergo programmed cell death. These targeted drugs have significantly changed the treatment landscape for SLL/CLL. For localized, symptomatic disease, radiation therapy may be used to shrink a bulky lymph node area.