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Why did this patient have a monocytosis and anaemia? Mantle cell lymphoma, under therapy
Folate deficiency
Post-infectious monocytosis
Chronic myelomonocytic leukaemia (CMML)

Online version of this month´s case:

The correct answer to September´s quiz is:

Mantle cell lymphoma, under therapy

Scattergrams and microscopy:

Patient history: a patient with a known disease, undergoing treatment.


Interpretation and differential diagnosis:

The answer can be inferred from… 

  • Anaemia: Low HGB, RBC and HCT
  • Sufficient haemoglobin incorporation during erythropoiesis: Normal MCH, MCHC, HYPO-He and RET-He
  • Inadequate erythropoiesis rate: RET#, RET% and IRF not increased
  • Presence of malignant lymphocytes: ‘Abn Lympho?’ flag
  • Absence of inflammatory response: No lymphocytosis, ‘Atypical Lympho?’ flag or antibody-synthesizing lymphocytes (AS-LYMPH% = 0.0)
  • Absence of dysplasia signs: Normal NEUT-GI


Case history

A 63-year old male patient suffering from mantle cell lymphoma had undergone chemotherapy and his blood was examined to monitor the effect of the treatment.


Case results

A normochromic, macrocytic anaemia was observed but the RBC indices that indicate haemoglobin incorporation during erythropoiesis (MCH, MCHC, MicroR, HYPO-He) were all normal. The RET% value was slightly increased but RET# and IRF were normal while MCV and MacroR were slightly increased, indicating an ineffective response to the anaemia caused by chemotherapy-related cell destruction. The WDF channel showed an abnormal lymphocyte population, which triggered a WPC reflex measurement. An abnormal, decreased W1/W2 ratio in the SSC-FSC scattergram of the WPC channel confirmed the presence of abnormal lymphocytes, generating an ‘Abn Lympho?’ flag. The blood smear showed mantle cell lymphoma cells with very heterogeneous morphology, which could be the cause of the false-high monocyte count from the WDF channel. However, a monocytosis as a side effect of the chemotherapy cannot be excluded.


The following answers are incorrect for the described reasons


Folate deficiency

The mild anaemia observed in this patient was not the result of poor haemoglobin incorporation during erythropoiesis because MCH, MCHC, HYPO-He and RET-He were all normal. Instead, it appeared to be associated with low RBC and HCT values, indicating either a loss of mature red blood cells or a decreased erythropoietic production rate. Like vitamin B12 deficiency, a shortage of folate (also called vitamin B9) results in impaired DNA synthesis and subsequent reduced cell proliferation. This leads to a macrocytic anaemia and, indeed, MCV was slightly increased here. However, the HYPER-He and MCH values were normal, the production of reticulocytes was not decreased and the immature platelet fraction was normal as well, indicating an unaffected thrombopoiesis rate. Therefore, a folate deficiency could be excluded.


Post-infectious monocytosis

The observed absolute monocytosis may be a response to either an infective / inflammatory condition or an underlying haematological malignancy. Reactive monocytosis is often associated with viral infections, or with chronic infections or inflammation. In such cases it would be associated with a significant inflammatory response and would have triggered a concomitant immune reaction. However, reactive signs such as a lymphocytosis, an increase of antibody-synthesizing cells (AS-LYMPH) or an ‘Atypical Lympho?’ flag were not present in this patient, which makes a reactive condition unlikely. The ‘Abn Lympho?’ flag pointed to a malignant condition instead.


Chronic myelomonocytic leukaemia (CMML)

CMML is a clonal disorder with myelodysplastic as well as myeloproliferative features. The haematological presentation is heterogeneous ranging from isolated monocytosis to myelodysplasia or from a mixed myelodysplastic / myeloproliferative disorder to a forthright myeloproliferative disorder with leukocytosis and splenomegaly, similar to chronic myeloid leukaemia. The diagnostic criteria for CMML include peripheral blood monocytosis in excess of 1000/µl as observed here, while the total leukocyte count may be increased, normal or decreased. However, the presence of abnormal lymphocytes rather than blasts, the absence of dysplasia signs (NEUT-GI is normal) and the high neutrophil to monocyte ratio (6.6 here but below 5 in CMML) made a CMML unlikely here.

Underlying disease:

Mantle cell lymphoma (1)

Mantle cell lymphoma (MCL) is an aggressive mature B cell non-Hodgkin lymphoma, characterised by the presence of small to medium-sized CD5-positive B-cells with irregular nuclei. Most patients initially present with lymphadenopathy but the gastrointestinal tract can also be involved. Like some other lymphomas, most MCL cases have the t(11;14)(q13;q32) chromosomal translocation that results in overexpression of cyclin D1. Differential diagnosis from other non-Hodgkin lymphomas such as follicular lymphoma, marginal zone lymphoma and lymphoblastic lymphoma is based on immunophenotyping and immunohistochemistry. Environmental risk factors for MCL are not known but genetics probably plays an important role: In the United States, whites are at a higher risk than African-Americans and men are affected three times as frequently as women.


Classification of lymphoid tumours



Lymphocytes (2)



Morphological classification




Immunological classification













Destroying cells that lack MHC-I molecules on their surface


Classification of lymphomas (3, 4, 5)



  1. Precursor lymphoid neoplasms
  2. Mature B-cell neoplasms
  3. Mature T-cell and NK-cell neoplasms
  4. Hodgkin lymphoma






  1. B lymphoblastic leukaemias/lymphomas
  2. T lymphoblastic leukaemias/lymphomas





  1. B-cell chronic lymphocytic leukaemia/small lymphocytic lymphoma
  2. B-cell prolymphocytic leukaemia
  3. Lymphoplasmacytic lymphoma
  4. Mantle cell lymphoma
  7. Nodal marginal zone lymphoma
  8. Splenic B-cell marginal zone lymphoma
  9. Hairy cell leukaemia
  10. Plasma cell myeloma
  11. Diffuse large B-cell lymphoma
  12. Primary mediastinal (thymic) large B-cell lymphoma
  13. Intravascular large B-cell lymphoma
  14. Primary effusion lymphoma
  15. Burkitt lymphoma





  1. T-cell prolymphocytic leukaemia
  2. T-cell large granular lymphocytic leukaemia
  3. Aggressive NK-cell leukaemia
  4. Mycosis fungoides
  5. Sezary syndrome
  6. Peripheral T-cell lymphoma, not otherwise characterised
  7. Hepatosplenic T-cell lymphoma
  8. Subcutaneous panniculitis-like T-cell lymphoma
  9. Angioimmunoblastic T-cell lymphoma
  11. Enteropathy-associated T-cell lymphoma
  12. Adult T-cell leukaemia/lymphoma
  13. Anaplastic large cell lymphoma, ALK positive/negative



Hodgkin lymphoma is subdivided into:


  1. Nodular lymphocyte-predominant Hodgkin lymphoma
  2. Classical Hodgkin lymphoma:


a)    Nodular sclerosis Hodgkin lymphoma

b)    Lymphocyte-rich classical Hodgkin lymphoma

c)    Mixed cellularity Hodgkin lymphoma

d)    Lymphocyte depletion Hodgkin lymphoma


  1. Schwerdlow SH, Campo E, Seto M et al (2007): Mantle Cell Lymphoma. In: Swerdlow SH, Campo E, Harris NL, et al (Editors): World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th Edition. Lyon, France. International Agency for Research on Cancer (IARC) Press: 229-232

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