Can lymphoma present with a normal peripheral blood smear (PBS)?

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Last updated: February 17, 2025View editorial policy

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From the Guidelines

Lymphoma can indeed present with a normal peripheral blood smear (PBS), as the disease often originates in lymphoid tissues and may not necessarily involve the peripheral blood [ 1 ]. In fact, many patients with lymphoma, particularly those with indolent subtypes such as follicular lymphoma, may have a normal complete blood count (CBC) and peripheral smear at diagnosis [ 1 ].

Key Points to Consider

  • Notably, even in cases where lymphoma cells are present in the blood, they may not be detectable on a routine peripheral smear, highlighting the importance of additional diagnostic testing, such as flow cytometry or bone marrow biopsy, to establish a definitive diagnosis [ 1 ].
  • The diagnosis of lymphoma should always be based on a surgical specimen/excisional lymph node biopsy, and a complete blood count, routine blood chemistry, and screening tests for HIV and hepatitis B and C are required [ 1 ].
  • Bone marrow biopsy is usually included in the workup for all patients with non-Hodgkin's lymphoma (NHL), except those with certain subtypes, and is essential for staging and restaging [ 1 ].
  • FDG-PET scan has been used for initial staging, restaging, and follow-up of patients with NHL, and is nearly universally positive at diagnosis in certain subtypes, such as Hodgkin lymphoma, DLBCL, and FL [ 1 ].

From the Research

Lymphoma Presentation

  • Lymphoma can present with a variety of symptoms and laboratory findings, including abnormalities on peripheral blood smears (PBS) 2, 3, 4, 5.
  • However, it is also possible for lymphoma to present with a normal PBS, as some cases may not have circulating lymphoma cells or may have a low level of involvement that is not detectable on a routine blood smear 3, 5.

Peripheral Blood Smear Findings

  • The presence of atypical lymphoid cells or smudge cells on a PBS can suggest lymphoma, but these findings are not specific and can be seen in other conditions as well 4, 5.
  • Flow cytometric immunophenotyping of peripheral blood can be helpful in diagnosing lymphoma, but it is not always possible to establish a definitive diagnosis based on PBS findings alone 2, 6, 4.

Diagnostic Challenges

  • The diagnosis of lymphoma often requires a combination of clinical, laboratory, and histopathological findings, and a normal PBS does not rule out the possibility of lymphoma 3, 4, 5.
  • Additional diagnostic tests, such as bone marrow biopsy, lymph node biopsy, and flow cytometry, may be necessary to establish a definitive diagnosis of lymphoma 2, 6, 4, 5.

References

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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