Anaplastic large cell lymphoma (ALCL) is diagnosed through a series of tests that examine the blood and bone marrow. The process usually begins with a physical examination where the doctor checks for physical signs of ALCL such as swollen lymph nodes in the neck, underarm and groin, as well as a swollen spleen or liver. If ALCL is suspected, the following tests may be conducted:

Blood Tests

• Complete blood count (CBC): A CBC measures the number of different types of blood cells, including red blood cells, white blood cells, and platelets. In ALCL, certain abnormalities in the CBC may be observed, such as anemia (low red blood cell count), leukocytosis (elevated white blood cell count), or eosinophilia (increased eosinophils), which is a type of white blood cell.
• Peripheral blood smear: A peripheral blood smear is a microscopic examination of a stained blood sample. It can reveal abnormalities in the appearance and shape of blood cells, which may provide clues about the presence of abnormal lymphocytes characteristic of ALCL.
• Liver and kidney function tests: Blood tests to assess liver function (liver enzymes) and kidney function (creatinine and blood urea nitrogen) may be performed to evaluate the overall health and detect any potential organ involvement or damage.
• Lactate dehydrogenase (LDH): LDH is an enzyme that is often elevated in the blood when there is tissue damage or cell turnover. Elevated LDH levels may be a nonspecific indicator of disease activity and can be seen in various medical conditions, including lymphomas.

Tissue Biopsy Tests

• Tissue biopsy: The initial step in diagnosing ALCL involves obtaining a tissue sample (biopsy) from an enlarged lymph node, skin lesion, or other affected site. The tissue is examined under a microscope by a pathologist, who can identify the characteristic features of ALCL, such as large, abnormal lymphoma cells with anaplastic morphology. 
• Immunophenotyping: To classify the specific subtype of ALCL and determine whether it is ALK-positive or ALK-negative, immunophenotyping is performed. This involves testing for the presence of specific markers (antigens) on the surface of the lymphoma cells. Major immunophenotypic features of ALCL include CD30+, CD15-, PAX-5-, and CD45+. Sixty percent of cases express 1 or more T-cell antigens (CD3+, CD43, or CD45RO). Anaplastic lymphoma kinase (ALK) protein may be detected in 60-70% of cases.
• Fluorescence in situ hybridization (FISH) test: FISH is able to find genetic abnormalities and helps identify the most common genetic changes a person with ALCL may have. The FISH test for ALCL can determine if a patient has ALK-positive or ALK-negative ALCL. It can also detect TP63 rearrangements which defines a subset of ALK-negative ALCL cases and are associated with aggressive course and poor outcome as compared to ALCL without these rearrangements

Imaging Tests

• Computed tomography (CT) scan: CT scans are commonly performed to evaluate lymphoma. A CT scan can help identify enlarged lymph nodes, assess organ involvement and detect masses or abnormalities in various areas.
• Positron emission tomography (PET) scan: A PET scan is often performed along with a CT scan and involves injecting a small amount of radioactive material into the bloodstream. Areas of increased metabolic activity, such as cancer cells will absorb more of the radiotracer and appear as "hot spots" on the scan. PET scans can help identify active lymphoma lesions, assess disease extent and guide treatment planning.
• Magnetic resonance imaging (MRI): MRI uses strong magnetic fields and radio waves to create detailed images of the body's soft tissues. It is particularly useful for assessing lymphoma involvement in the central nervous system (CNS) or musculoskeletal system.
• Ultrasound: Ultrasound imaging may be used to evaluate lymph nodes close to the body's surface, such as those in the neck, armpits, or groin. It can help assess the size and characteristics of lymph nodes and other structures.
• Bone scans: In cases where bone involvement is suspected, a bone scan may be performed. A small amount of radioactive material is injected into the bloodstream, and a special camera detects areas of increased or abnormal bone activity.
• Chest X-ray: A chest X-ray may be used to assess the chest area and detect any abnormalities, such as enlarged lymph nodes or lung involvement.

It's important to note that the diagnosis and classification of ALCL is complex and requires a comprehensive evaluation by a team of specialists. A complete diagnosis requires a physical examination, looking at a tissue biopsy sample under the microscope, immunophenotyping, and genetic testing. The specific markers and genetic changes found in the sample can also help determine a person's prognosis and guide treatment decisions. If you don't currently have an ALCL specialist on your team, it is important that you consult with one. Use HealthTree's ALCL Specialist Directory to locate a specialist near you. 

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