Your pathology report for atypical lymphoid infiltrate

by Jason Wasserman MD PhD FRCPC and Kamran M. Mirza MBBS PhD
September 9, 2025

Atypical lymphoid infiltrate is a descriptive, often preliminary diagnosis. Atypical means that the cells do not look normal (hence they are not typical or usual), but they are also not clearly cancerous. Lymphoid refers to lymphocytes, a type of white blood cell that is part of the immune system. It means the biopsy shows an unusual collection of lymphoid cells, but the sample does not provide sufficient clear information to determine whether the process is reactive (noncancerous) or a lymphoma (a type of cancer). In other words, the findings are not normal, but they are not definitive. By making this diagnosis, your pathologist is telling your care team that more information or testing is needed before a final diagnosis can be made.

What are the potential causes?

An atypical lymphoid infiltrate can be caused by both noncancerous and cancerous conditions. The challenge is that small biopsies sometimes cannot clearly separate these possibilities.

Noncancerous conditions

Noncancerous causes are often called “reactive” changes. These are responses of the immune system to infection, injury, or irritation. Reactive infiltrates can be seen in:

  • Swollen lymph nodes from a recent infection.

  • Inflamed skin or bowel tissue.

  • Reactions to foreign material, such as tattoo pigment or a tick bite.

In reactive conditions, the infiltrate is usually a mix of different immune cells, and the process does not behave like cancer.

Cancerous conditions

Cancerous causes include different types of lymphoma. These are cancers of lymphocytes. Examples include:

Symptoms of an atypical lymphoid infiltrate

The symptoms depend entirely on the site and the underlying cause. Many patients have no symptoms, and the finding is discovered incidentally.

  • In lymph nodes, patients may notice painless swelling or enlarged nodes. Some may have fevers, night sweats, or weight loss if the cause is lymphoma.

  • In the skin, patients may see or feel plaques, nodules, or patches, which can be itchy or tender.

  • In the gastrointestinal tract, patients may have abdominal pain, bleeding, or a polyp or mass seen during endoscopy.

  • In soft tissue or the peritoneum, patients may feel a mass or pressure.

Because the causes are so varied, the symptoms alone cannot confirm whether the process is reactive or a lymphoma.

Does atypical lymphoid infiltrate mean cancer?

No. The term itself does not mean cancer. It means the findings are unusual but not specific. Some cases turn out to be reactive once all the tests are done, while others turn out to be lymphoma. Your pathologist is leaving the door open until more information is available.

What does it mean if the report says suspicious for lymphoma?

“Suspicious for lymphoma” means the biopsy has several features that strongly suggest lymphoma, but the tissue is too limited to be sure. This may happen if there are only small cores, if the sample is crushed, or if the key cells are rare. In this situation, your doctor may recommend a larger biopsy, often an excisional biopsy, to provide enough tissue for a definite diagnosis.

What does it mean if the report says favor reactive?

“Favor reactive” means that the overall appearance looks more like a noncancerous immune response. The cells are mixed and the tissue structure looks more natural. Even so, pathologists are careful. Sometimes more tests or follow-up are still recommended to be safe.

What types of cells may be seen in an atypical lymphoid infiltrate?

An atypical lymphoid infiltrate may contain a variety of immune cells. What is seen can provide important clues.

  • B cells are a type of lymphocyte. They may appear as small mature cells, or as larger atypical cells in some lymphomas. In tissues like the bowel, they can push into glands and form small clusters called lymphoepithelial lesions.

  • T cells are another type of lymphocyte. They may form most of the background in some samples, and in skin they may cluster around hair follicles.

  • Plasma cells are mature lymphocytes derived from B cells that make antibodies. They can be numerous in reactive conditions, but they can also appear in certain low-grade lymphomas.

  • Histiocytes are a kind of tissue macrophage. They may form nodules or mix with eosinophils, which are another type of immune cell.

  • Large atypical cells may also be seen. When they resemble Hodgkin cells, classic Hodgkin lymphoma is considered. Larger scattered B cells in a background of T cells can suggest entities such as T-cell histiocyte-rich large B-cell lymphoma.

Pathologists look at the mix and pattern of these cells to guide the next steps.

What other tests may be performed to confirm the diagnosis?

Pathologists often order additional tests to better understand an atypical lymphoid infiltrate. These tests help decide whether the process is reactive or a lymphoma.

Immunohistochemistry

Immunohistochemistry (IHC) uses stains to highlight specific proteins in the tissue. It helps identify which cells are B cells, which are T cells, and whether the patterns match known types of lymphoma.

Flow cytometry

Flow cytometry is performed on fresh tissue. It studies thousands of single cells and looks for evidence that the B cells or T cells are all the same (clonal) or a mix (polyclonal). A clonal result supports lymphoma, while a polyclonal result supports a reactive process.

Molecular clonality testing

Clonality testing looks at the genetic material of B cells or T cells. A clonal result means the cells are copies of each other and supports lymphoma. A nonclonal result means the cells are diverse, supporting a reactive process. These results must always be interpreted with the microscope findings and other tests, because false positives and negatives are possible.

In situ hybridization

In situ hybridization (ISH) can look at light chains (kappa and lambda) on plasma cells to see if one type is more common than the other, which suggests clonality. It can also be used to detect viruses such as Epstein–Barr virus (EBV) in the tissue.

Special stains or cultures

If infection is suspected, special stains or microbiology tests may be ordered to look for bacteria, fungi, or mycobacteria.

Repeat biopsy

Sometimes the most important next step is a repeat biopsy that provides more tissue. Larger samples (such as an excisional biopsy) allow the pathologist to see the tissue structure and to run all of the necessary tests.

Conditions associated with specific areas of the body

The significance of an atypical lymphoid infiltrate depends on where in the body it is found. Some locations have characteristic conditions that your doctor and pathologist will consider.

Lymph nodes

In lymph nodes, atypical infiltrates may represent reactive changes after infection or different types of lymphoma. Both B-cell and T-cell lymphomas, as well as classic Hodgkin lymphoma, are possible. Sometimes only a larger excisional biopsy can show the full architecture needed for diagnosis.

Skin

In the skin, atypical infiltrates may represent reactive conditions, cutaneous B-cell processes such as marginal zone lymphoproliferative disorders, or cutaneous T-cell lymphoma such as mycosis fungoides. Repeated biopsies are sometimes needed because small samples may not be conclusive.

Gastrointestinal tract

In the bowel, atypical B-cell infiltrates may suggest marginal zone lymphoma of mucosa-associated lymphoid tissue, but they can also be reactive changes. The presence of lymphoepithelial lesions or light chain restriction increases concern for lymphoma, and molecular clonality testing is often used.

Questions to ask your doctor

  • Does my biopsy look more reactive or more suspicious for lymphoma at this point?

  • Do I need a larger or repeat biopsy, and should part of the sample be sent fresh for flow cytometry?

  • What additional tests are being done, and when will the results be available?

  • What would it mean if the results are clonal or nonclonal?

  • Should I see a hematologist now, or wait for more information?

  • If the findings are reactive, how will we follow up?

  • If the findings are lymphoma, what type is most likely and what would the next steps in treatment be?

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