Sysmex Sverige
Sysmex Europe
Other Sites
Menu

Do you know which disease fits this month’s case? Then test your knowledge in the quiz below!

Which condition caused the observed lymphocytosis? T-acute lymphoblastic leukaemia
Benign monoclonal B-cell lymphocytosis
Acute phase of infectious mononucleosis
B-cell chronic lymphatic leukaemia (B-CLL)

Online version of this month´s case:

The correct answer to October´s quiz is:

Benign monoclonal B-cell lymphocytosis

Scattergrams and microscopy:

Patient history: a 32-year old woman with light fatigue was referred to the hospital for further investigation of a detected lymphocytosis.

Table:

Interpretation and differential diagnosis:

The answer can be inferred from…

  • Absolute and relative lymphocytosis: LYMPH# = 7.46 x 109/L and LYMPH% = 66.5%
  • Absence of reactive or malignant lymphocytes: Low Re-LYMPH#/% and AS-LYMPH#/% values, no ‘Atypical Lympho?’, ‘Abn Lympho?’ or ‘Blasts?’ flag after WPC measurement
  • CD-marker profile
  • No anaemia or thrombocytopenia

 

 

Case history

A 32-year old woman visited her physician complaining about persistent but light fatigue. After a lymphocytosis was observed in an otherwise normal complete blood count, she was referred to the hospital for further investigation.

 

Case results

The complete blood count results looked normal except for the absolute and relative lymphocytosis. The position of the lymphocyte population in the WDF scattergram was normal: side fluorescence (SFL) and side scatter (SSC) were neither increased nor decreased. Consequently, the reactive lymphocyte count was zero (Re-LYMPH% = 0%) and the ‘Abn. Lympho?’ flag was not triggered by the WPC channel. The immune flow cytometry showed that 28% of all white blood cells expressed the CD19 B-cell marker and almost all of these also expressed CD20. A weak CD5 expression on 71% of B-cells also observed, which can be a sign of B-CLL. However, weak expression of FMC7, which is typically absent in B-CLL, was also detected in 60% of B-cells. The kappa/lambda ratio was very high in this patient, which confirmed the presence of a monoclonal B-lymphocytes population. The final diagnosis was a benign monoclonal B-cell lymphocytosis.

 

 

The following answers are incorrect for the described reasons

 

T-acute lymphoblastic leukaemia (T-ALL)

T-ALL represents 20-30% of all acute lymphoblastic leukaemia cases and is associated with a poor prognosis. It is characterized by symptoms related to anaemia, thrombocytopenia, and neutropenia due to infiltration of the bone marrow with tumour cells. T-lymphoblasts present in T-ALL samples appear as an abnormal population between the lymphocytes and monocytes in the WDF scattergram and these T-lymphoblasts, which are larger and have a different membrane lipid composition than other lymphocytes, are also visible in the SSC-FSC scattergram of the WPC channel where they trigger the appearance of a ’Blasts?’ flag. There were no such cells in the presented sample and this patient was not anaemic, thrombocytopenic or neutropenic so a T-ALL was very unlikely. In addition, the immunophenotype of this patient showed proliferation of mature B-cells, which excludes a T-ALL.

 

Acute phase of infectious mononucleosis

During an infection the cellular immune response by lymphocytes results in a lymphocytosis, as observed here. However, it is also associated with a large increase of reactive lymphocytes (Re-LYMPH% > 5% and appearance of the ‘Atypical Lympho?’ flag), which would be visible in the WDF scattergram due to their increased fluorescence intensity. In addition, the population of lymphocytes with increased membrane lipids (activated T-cells), which is in the lower lymphocyte population in the SSC-FSC scattergram of the WPC channel, would have been bigger. Therefore, this diagnosis was very unlikely.

 

B-cell chronic lymphatic leukaemia (B-CLL)

B-CLL is a chronic lymphoproliferative disorder with lymphocyte counts usually above 5,000/µL (7,460/µL here) and the WDF scattergram of samples obtained from B-CLL patients looks very similar to the one presented here. However, only lymphocyte counts above 10,000/µL strongly suggest a B-CLL so the count observed here was relatively low, unless the condition was detected at a very early stage. Immune flow cytometry showed that 28% of all white blood cells expressed the B-cell marker CD19: 3,140 B-cells/µL. Of these 71% had weak expression of CD5 (2,230/µL), which is normally only found on T-cells but is also expressed by some B-cells in B-CLL (although usually at a higher concentration of at least 5,000 CD5-positive B-cells/µL). These criteria were not enough to exclude a B-CLL yet but combined with the expression of FMC7 (typically absent in B-CLL) make this diagnosis unlikely.

Underlying disease:

Benign monoclonal B-cell lymphocytosis

Benign MBL is characterized by the presence of low numbers of monoclonal B-cells that usually have chronic lymphocytic leukaemia (CLL) characteristics in the peripheral blood of healthy individuals with absolute lymphocyte counts that are elevated but typically below 5,000/µL. Red blood cell and platelet counts are normal while lymphadenopathy, organomegaly and other disease-related symptoms are absent in such individuals who may remain asymptomatic for life (1, 2).

 

The following diagnosis criteria were proposed by Marti et al in 2005 (2):

1.    The presence of a monoclonal B-cell population in the peripheral blood with either

a.    A high or low kappa/lambda ratio (>3:1 or <0.3:1)

b.    More than 25% of B cells without or with low level surface immunoglobulin

c.    A disease-specific immunophenotype

2.    Continuous presence of the monoclonal B-cell population during a 3-month period

3.    Absence of:

a.    Lymphadenopathy and organomegaly

b.    Autoimmune disease or infection

c.    B-cell count >5,000/µL

d.    Any other indication of a B-cell lymphoproliferative disorder

 

Although more than one in seven relatives of CLL patients have benign MBL, the incidence of benign MBL in the general population is estimated to be around 3% but it increases with age (1, 3): 0.3% of persons under 40 years old are affected, 2.1% of persons between 40 and 60, 5.0% of persons over 60 and 50-75% of persons over 90. Men are approximately two times more-likely to have benign MBL than women. The immunophenotype and genetic abnormalities of benign MBL B-cells can resemble those of CLL B-cells but only 1-2% of benign MBL patients progresses to CLL every year. An effective treatment to prevent this is not available and it is currently not possible to predict which patients are at risk of malignant progression, which makes dealing with a benign MBL diagnosis difficult for doctors and patients alike.

Literature:

  1. Ghia P, Caligaris-Cappio F (2012): Monoclonal B-cell lymphocytosis: right track or red herring? Blood 119(19): 4358-4362
  2. Marti GE, Rawstron AC, Ghia P et al (2005): Diagnostic criteria for monoclonal B-cell lymphocytosis. Br J Haematol 130(3): 325–332
  3. Rawstron AC, Green MJ, Kuzmicki A et al (2002): Monoclonal B lymphocytes with the characteristics of ‘‘indolent’’ chronic lymphocytic leukemia are present in 3.5% of adults with normal blood counts. Blood 100(2): 635–639

Sysmex parameters

Our Glossary

An alphabetical listing of scientific terms

Explore our Glossary

Download our Wallpaper 2015

Enjoy our Media Center
All
  • All
  • Documents
  • Podcast
  • Images
  • Videos
Company movie
See our collection
See our collection http://www.sysmex.se/academy.html
See our collection http://www.sysmex.se/academy.html
Grow your knowledge http://www.sysmex.se/academy/knowledge-centre.html
See our library of smears http://www.sysmex.se/academy/library/image-gallery.html
Learn more about our concept http://www.sysmex.se/company/who-is-sysmex/silent-design.html