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Reactive white-cell patterns and inherited anomalies

15 min

  • Recognize reactive neutrophilia from a left shift and toxic changes
  • Recognize a heterogeneous reactive lymphocyte population
  • Distinguish an inherited leukocyte anomaly from a reactive or clonal change
  • Report a CBC and film as compatible with a disorder until confirming tests are done

Read the full reference

Try first

Try first

A differential shows neutrophilia with a left shift, toxic granulation, and Döhle bodies. Basophils and eosinophils are not increased. Does this fit a leukemoid reaction or a chronic myeloid leukemia (CML) pattern?

The next section explains it.

Right. The next section explains why.

The next section explains it.

The next section explains it.

Get the idea

A left shift with toxic changes

A leukemoid reaction is marked reactive neutrophilic leukocytosis, traditionally a WBC count above 50 × 10³/µL with a left shift, seen with severe infection, inflammation, metabolic stress, growth-factor exposure, or a cytokine-secreting tumor.1 Toxic granulation, Döhle bodies, and vacuoles often accompany it, and persistent basophilia and eosinophilia together are usually absent. CML shows a broad granulocytic maturation spectrum with basophilia, often with eosinophilia too, and needs a BCR::ABL1 result to establish it.3

A population that varies from cell to cell

Reactive lymphocytes vary from cell to cell in size, nuclear shape, chromatin density, and cytoplasmic basophilia, and their cytoplasm often molds around adjacent red cells.1,2 A clonal population repeats similar cells across the film. ICSH recommends "reactive lymphocyte" for a benign-appearing varied population and "abnormal lymphocyte" with a description when a clonal process is suspected. Morphology directs follow-up, and flow cytometry establishes clonality.2

An inherited pattern versus an acquired one

An inherited leukocyte anomaly persists across serial specimens and family members. A reactive change comes and goes with illness and recovery.1 Pelger-Huët nuclei are mature, with coarse clumped chromatin in two rounded lobes or a band-like shape. Counting them as bands or metamyelocytes creates a false left shift. May-Hegglin inclusions appear in several leukocyte lines together with giant platelets. A true Döhle body is seen in neutrophils and comes with infection.4

Report the pattern as compatible

A CBC and film finding is reported as compatible with a pattern until confirming tests are done. A CML-compatible film still needs a BCR::ABL1 result, and a reactive-appearing population still needs the clinical setting and, when uncertain, a clonality study, before the pattern becomes a diagnosis.3

References
  1. Keohane EM, Preston MM, Mirza KM, Walenga JM, eds. Rodak's Hematology: Clinical Principles and Applications. 7th ed. Elsevier; 2025. Accessed September 26, 2026. https://www.us.elsevierhealth.com/rodaks-hematology-9780323936507.html
  2. Palmer L, Briggs C, McFadden S, et al. ICSH recommendations for the standardization of nomenclature and grading of peripheral blood cell morphological features. Int J Lab Hematol. 2015;37(3):287-303. doi:10.1111/ijlh.12327
  3. Apperley JF, Milojkovic D, Cross NCP, et al. 2025 European LeukemiaNet recommendations for the management of chronic myeloid leukemia. Leukemia. 2025;39(8):1797-1813. doi:10.1038/s41375-025-02664-w
  4. MYH9-related disease. GeneReviews. Accessed September 26, 2026. https://www.ncbi.nlm.nih.gov/books/NBK2689/

Watch one

A differential on a 68-year-old man with fever and a productive cough shows a WBC count of 62 × 10³/µL, a left shift with metamyelocytes and myelocytes, and toxic granulation. Basophils and eosinophils are not increased. What do you report?

  1. Read the film: a left shift with metamyelocytes and myelocytes, and toxic granulation.

    Morphology is read before any cause is assigned to it.

  2. Check for basophilia and eosinophilia: neither is increased.

    Persistent basophilia with eosinophilia is what separates a CML pattern from a leukemoid reaction.

  3. Read the order's clinical note: fever and a productive cough fit a reactive cause.

    The clinical note tells you whether a reactive stimulus is present.

  4. Word the report as a pattern compatible with a leukemoid reaction.

    The film alone cannot rule CML in or out, so the wording stays at compatible.

Report a neutrophilic leukocytosis with a left shift and toxic granulation, compatible with a leukemoid reaction, and note that basophils and eosinophils are not increased. A BCR::ABL1 result settles CML if the pattern persists.

Your turn

Problem 1 of 3

A film shows lymphocytes that vary in size, chromatin density, and cytoplasmic basophilia, some molding around adjacent red cells. Which term is recommended, and which laboratory action follows?

Incorrect. ICSH lists atypical, variant, and Downey cell as historical, inconsistent terms. A varied population supports a benign stimulus, and flow cytometry is selected for a persistent uniform abnormal population.

Correct. ICSH recommends reactive lymphocyte when morphology supports a benign stimulus. The laboratory correlates the finding with the clinical setting and with targeted infectious or drug testing.

Incorrect. Abnormal lymphocyte, with a description, is used when a clonal process is suspected, as with a persistent uniform population. Variation from cell to cell points to a reactive population.

Hint
  1. Look at whether the cells repeat the same appearance or vary from one to the next.
  2. One term points to a benign stimulus. The other points to a possible clone and a laboratory study.

Review Reactive lymphocyte patterns

Problem 2 of 3

Most neutrophils on a film show bilobed pince-nez nuclei with coarse chromatin, and the patient is well. How are these cells classified on the differential?

Incorrect. Calling Pelger-Huët cells bands invents a left shift and can suggest infection or a myeloid neoplasm that is not there.

Incorrect. Coarse chromatin in two rounded lobes marks mature neutrophils with reduced segmentation. Counting them as an immature stage invents a left shift.

Correct. Inherited Pelger-Huët anomaly typically affects most neutrophils, and their function is preserved. The comment names the anomaly. Persistence, family findings, medication history, and other dysplasia direct any further investigation.

Hint
  1. Look at the chromatin as well as the nuclear shape.
  2. Coarse, clumped chromatin marks a mature nucleus.

Review Nuclear segmentation anomalies

Problem 3 of 3

A blood film in a patient with unexplained pallor shows findings compatible with iron deficiency, and the report states this. No ferritin or iron studies have been ordered yet. Is the report complete?

A film compatible with iron deficiency can also fit other causes of a microcytic, hypochromic pattern. Ferritin and iron studies are what confirm it.

Reported a CBC or film finding as a final classification

A CBC or film pattern can be compatible with CML, CLL, iron deficiency, or B12 deficiency and still need ferritin, B12, flow cytometry, or genetic results before a diagnosis is made. Reporting the film finding as the diagnosis skips those tests.

The film supports a pattern compatible with iron deficiency. Ferritin, transferrin saturation, or TIBC are needed before the cause is confirmed.

Film morphology is a useful part of an anemia workup. It supports a pattern. It does not replace the confirming laboratory studies.

Review Reactive lymphocyte patterns

Use it

Try this at the MicroscopePendingWBC0 / 100PENDINGPeripheral blood differentialPerform manual diff

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