Lymphocytosis

This guideline applies to adults

Introduction

Lymphocytosis is a common finding. Causes may include acute viral, bacterial (eg pertussis) or protozoal (eg toxoplasmosis) infection. Viral infection usually causes a modest and temporary (<2 months) rise in lymphocytes.

Other causes include malignancy (most commonly CLL), other low grade lymphoproliferative disorders, and smoking.

Less common causes include auto-immune disease, medication and stress (eg extreme exercise, cardiac or trauma, previous splenectomy and obesity).

In scope

Lymphocytosis

Not in scope

Other haematological conditions

Red Flag Features

Features of an acute leukaemia on blood film
B symptoms (eg involuntary weight loss, night sweats)

*This list is non exhaustive

Investigations required prior to referral

Consider reactive causes.

Following initial detection of lymphocytosis, in an otherwise well patient with no red flags or reactive causes, repeat FBC in 2-3 months time. If lymphocytosis persists, examine for lymphadenopathy and splenomegaly.

If the patient is unwell, request a blood film and consider testing for EBV, CMV and HIV serology for IgM and IgG antibodies

NB. The EBV screen (Monospot or Paul Bunnell) gives both false positive and false negative results and requesting serology for IgG and IgM antibody is preferable and specific.

Management optimisation

Treat and manage any underlying acute infection as appropriate.

CLL is the most common cause of malignant lymphocytosis. Asymptomatic CLL does not benefit from early treatment. Lymphocytosis without symptoms or a known cause can reasonably be monitored in the community with a second FBC after 2 months and then annually.

Encourage smoking cessation as appropriate.

Advice and Guidance

Haematology A&G can be accessed via ERS: Haematology Advice & Guidance

This service should not be used for suspected fast track referrals.

Referral

Emergency referral criteria

If a blood film suggests an acute leukaemia arrange an immediate admission via the medical team.

Urgent referral criteria

CLL is not usually an indication for an urgent fast track referral but seek haematology advice is the patient is significantly unwell (for example if there are new or significant B symptoms, or rapidly enlarging lymph nodes). Haematology advice and guidance is answered within 24 hours, but depending on clinical judgement if the patient is too unwell to wait for this, consider admission via the medical admissions team.

Routine referral criteria

Refer routinely to Haematology if lymphocytosis and:

Significant and persistent (> 4 weeks) lymphadenopathy in the absence of a secondary cause
Splenomegaly
Systemic symptoms
Unexplained anaemia (Hb <100g/L) or thrombocytopenia (Platelets < 100)
Progressive lymphocytosis with an increase of ≥50% over a 3-month period or lymphocyte doubling time of <6 months (patients with a lymphocyte count < 30 may require a longer observation period to determine doubling time).

Known CLL

If CLL is being monitored in the community already then referral or discussion with haematology is indicated if:

the lymphocyte count is rising rapidly e.g. an increase of ≥50% over a 2-month period or lymphocyte doubling time of <6 months (NB. patients with a lymphocyte count < 30 may require a longer observation period to determine doubling time).
the patient is systemically unwell (eg involuntary weight loss, night sweats)
clinically significant and persistent lymphadenopathy
clinically palpable splenomegaly
other components of the blood count are abnormal (eg anaemia, thrombocytopenia)

Supporting Information

For professionals

Chronic Lymphocytic Leukaemia | Doctor

For patients

References

Peninsula Cancer Alliance, Haematology Site Specific Group, Advice and Guidance for non-haematological conditions, October 2024

Page Review Information

Review date	08 July 2025
Next review date	08 July 2027
Clinical editor	Dr L Lomas, RMS GP
Contributors	Peninsula Cancer Alliance, Haematology Site Specific Group Dr Michelle Furtado