GP Connect is an initiative to facilitate a broader understanding of laboratory testing by focusing on common enquires between General Practitioners and Pathologists at Australian Clinical Laboratories. In this edition, Clinical Labs' haematologist/pathologist, Associate Professor Chris Barnes, responds to questions asked by general practitioner, Dr Jon Barrell, about the topic of lymphocyte surface markers.
A/Prof Chris Barnes
(Pathologist)
MBBS, FRACP, FRCPA
A/Prof Chris Barnes is a clinical and laboratory trained haematologist and the National Director of Haematology at Australian Clinical Labs. He also works as director of the Haemophilia Treatment Centre at the Royal Children’s Hospital, Melbourne. A/Prof Barnes has an active clinical research interest and is also director of Melbourne Haematology (Clinical) and Melbourne Paediatric Specialists.
Dr Jon Barrell
(General Practitioner)
MBBS, DRACOG, FRACGP
Dr Jon Barrell is founding principal of Springs Medical and works full-time between the Daylesford and Trentham clinics. He is also Conjoint Senior Clinical Lecturer in the School of Medicine, Faculty of Health at Deakin University. Dr Barrell enjoys teaching medical students and GP Registrars, and has been a FRACGP Examiner and Vice Chairman of the Ballarat and District Division of General Practice.
Dr Jon Barrell (General Practitioner)
I have a 65-year-old patient who has mild lymphocytosis – what tests should I order next?
A/Prof Chris Barnes (Pathologist)
Lymphocytosis is commonly picked up by a screening test and is often the transient result of a viral infection. However, lymphocytosis that is still persistent after six weeks needs further assessment to rule out an emerging lymphoproliferative disorder. The next step is to order lymphocyte surface markers. Lymphocyte surface markers are used to determine if there is an abnormal (clonal) population of lymphocytes present in the peripheral blood. The test relies on fixing antibodies to cell surface markers and looking for a particular monoclonal population.
Dr Jon Barrell (General Practitioner)
What does it mean if there is a monoclonal population on lymphocyte surface markers?
A/Prof Chris Barnes (Pathologist)
The presence of a monoclonal population may mean that the patient has indicators of an early lymphoproliferative disorder, e.g., lymphoma or chronic lymphocytic leukaemia (CLL). Whilst this sounds bad, many lymphoproliferative disorders are very low-grade and may not need any treatment; monitoring of the patient is all that is required. Other lymphoproliferative disorders may require early therapy. Referral to a haematologist is generally recommended.
Dr Jon Barrell (General Practitioner)
What if the lymphocyte surface markers are negative and the patient still has lymphocytosis?
A/Prof Chris Barnes (Pathologist)
Lymphocyte surface markers is a good test for B-cell lymphoproliferative disorders. However, lymphocyte surface markers may not be abnormal in T-cell lymphoproliferative disorders (T-cell disorders are much
less common). T-cell disorders may require additional testing (e.g. T-cell receptor rearrangement). Other causes of lymphocytosis include hyposplenism, recurrent viral infections, some autoimmune disorders and other malignancies. Smoking may also cause a low-level lymphocytosis. If the cause for lymphocytosis is not clear, ongoing monitoring, repeat assessment of lymphocyte surface markers or referral to a haematologist may be helpful.
Dr Jon Barrell (General Practitioner)
In practice, I find CLL the most common cause of chronic lymphocytosis in older patients, and I find lymphoma more commonly presents as a mass lesion without lymphocytosis. Am I correct?
A/Prof Chris Barnes (Pathologist)
CLL is a very common cause of lymphocytosis in the aging population with the average age, at the time of diagnosis of CLL, being around 70 years. CLL is uncommon in patients less than 40 years of age. Somewhat confusingly, the term small lymphocytic lymphoma (SLL) refers to patients who have cells with the same morphology and immunophenotype of CLL within lymph nodes or other tissues, but these cells are not present in the peripheral blood.
Other lymphoproliferative disorders present less commonly with lymphocytosis. Follicular lymphoma and diffuse large B-cell lymphoma (DLBCL) collectively represent approximately two thirds of all adult non-Hodgkin’s lymphoma. These lymphoproliferative disorders may present with isolated lymph node enlargement (e.g. follicular lymphoma) or extra nodal mass lesions (e.g. DLBCL). Follicular lymphoma in particular often presents in younger adult patients with a median age in the 6th decade.
Dr Jon Barrell (General Practitioner)
What if the lymphocyte surface markers are negative, but I am suspicious the patient has CLL or another lymphoma?
A/Prof Chris Barnes (Pathologist)
Lymphocyte surface markers are a sensitive test – many millions of cells are analysed during each assessment using modern flow cytometry methods. Detecting monoclonal populations or populations of cells that express usual antigens is the focus of flow cytometry techniques. Specially trained flow cytometry scientists run these tests using standard operating procedures and carefully controlled and calibrated methods. Isolated results of single tests should, however, never replace clinical experience. Should there be a discrepancy between the results and the clinical findings of the patient, I would suggest calling your local haematologist to discuss your concerns. Repeat, or additional tests (e.g. T-cell receptor rearrangement studies or molecular testing) may be indicated.
