8/3/2019 CLL With Unusual Granulation

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Chronic (B cell) lymphocytic leukaemia with unusual granulation

A 79-year-old patient with chronic lymphocytic leukaemia

(CLL), in whom the neoplastic B lymphocytes from peripheral

blood (PB) and bone marrow showed intracellular granules, is

described. The diagnosis of CLL had been made in 1992(clinical stage Rai 0, Binet A). The patient remained asymp-

tomatic without any need for treatment until 5 years before

this presentation, when a significant enlargement of lymph

nodes in several areas was noted. Combination chemotherapy 

(CHOP: cyclophosphamide, doxorubicin, vincristine and

prednisone) was started and subsequently replaced by a 3- to

4-weekly dose of cyclophosphamide and intermediate dose

prednisone. Clinical progression was evident over a period of 

several months, with increasing lymphocytosis and lympha-

denopathy, unresponsive to chemotherapy. At this stage, an

automatic blood cell count (Advia-120; Bayer, Leverkusen,

Germany) showed a high leucocyte count (77.8 · 109/l) and

anaemia (haemoglobin, Hb: 9.9 g/dl) with a normal platelet

count. A PB film showed 96% lymphocytes with 90% of these

containing variably sized, round, azurophilic cytoplasmic

granules (left). Some cells also showed small vacuoles.

Neoplastic lymphocytes did not show acid hydrolases on

cytochemical staining. Immunophenotyping showed that 95%

of lymphocytes expressed a characteristic CLL phenotype: B

lineage (CD19) with co-expression of CD23 and CD5 and

weak expression of CD20, CD22 and CD79b. The neoplastic

population showed co-expression of immunoglobulin (Ig)D

and IgM, a restricted lambda light chain pattern and high

expression of CD38 (>30%) and ZAP-70 (>20%). Cytogeneticanalysis showed t(1;4)(q31;q33) and trisomy 12. Transmission

electron microscopy (TEM) showed that PB lymphocytes

contained variably sized, irregular, dense, cytoplasmic granules

(right, TEM · 10 000). The incidence of cytoplasmic inclu-

sions in CLL lymphocytes is very low: membrane-bound

vacuoles and crystal-like or filamentous inclusions have

occasionally been reported. An immunoglobulin origin of the

very unusual cytoplasmic granules in this patient is highly 

probable.

Anna Merino1

Marıa Rozman2

Jordi Esteve3

1Department of Haemotherapy-Haemostasis, Hospital Clınic, Centro de

Diagnostico Biomedico (CDB), Barcelona, 2Haemopathology Unit,

Hospital Clınic, CDB, Barcelona, and  3Hospital Clınic, Haematology 

Department, Barcelona, Spain

E-mail: amerino@clinic.ub.es

images in haematology

doi:10.1111/j.1365-2141.2006.06039.x ª 2005 Blackwell Publishing Ltd, British Journal of Haematology , 133, 354