Leukaemic Monocytoid Marginal Zone Lymphoma (LMMZL): A Rare Undescribed Lymphoproliferative Disorder with Unique Features.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4424-4424
Author(s):  
Lara N. Roberts ◽  
Madan M. Ryali ◽  
Stella J. Bowcock ◽  
Susan M. Ward ◽  
Richard Gale ◽  
...  

Abstract We report five cases of clonal lymphocytosis with striking monocytoid features, immunophenotype and clinical features distinct from chronic lymphocytic leukaemia (CLL), splenic marginal zone lymphoma (MZL) also known as splenic lymphoma with villous lymphocytes (SLVL) and mantle cell lymphoma (MCL). We believe these cases to represent a unique leukaemic variant of monocytoid MZL. All cases presented with marked peripheral blood lymphocytosis, no smear cells and monocytoid morphology with voluminous sometimes vacuolated cytoplasm. Immunophenotyping confirmed clonal lymphocytosis with strong light chain restriction, positivity for CD19 and CD20, absent or weak expression of CD10, CD22, CD23 and FMC7 and variable but weak CD5 expression. Bone marrow trephine biopsies revealed marked hypercellularity with a non-nodular diffuse lymphoid infiltrate. Cytogenetic analysis in cases 1 and 5 was normal, and fluorescent in-situ hybridisation (FISH) for abnormalities associated with CLL (11q23, trisomy 12, 13q14 and 17p13) and MCL (t11,14) were negative. Case 1: A 70 year old male presented with symptoms of anaemia, generalised lymphadenopathy, splenomegaly and leucocytosis. He progressed through chlorambucil and prednisolone but responded to oral fludarabine. He has been successfully retreated with fludarabine on relapse and remains alive, more than six years post diagnosis. Case 2: A 79 year old female was admitted with abdominal pain and vomiting. Investigation revealed marked leucocytosis with grossly abnormal liver function tests. This patient’s condition deteriorated rapidly and she died before intervention was possible, ten days post presentation. Case 3: An 87 year old female presented with an incidental finding of lymphocytosis and isolated splenomegaly. Six months following her presentation she developed anaemia, thrombocytopenia and progressive lymphocytosis. Her disease progressed through chlorambucil and cyclophosphamide but responded to fludarabine. She unfortunately died of a cerebrovascular accident, eighteen months after diagnosis. Case 4: A 72 year old female presented with B symptoms, axillary lymphadenopathy and massive splenomegaly. She developed progressive B symptoms and rapid doubling of her white cell count, necessitating initiation of treatment. Despite an initial partial response to chlorambucil and prednisolone, her disease continued to progress and was refractory to multiple lines of chemotherapy. She died six years after her initial presentation. Case 5: An 84 year old presented with mild anaemia and leucocytosis and had clinical splenomegaly. He was managed with supportive therapy only and died of unrelated causes. Summary: The clinical presentation of these cases mimics that of CLL. The morphology of the peripheral blood lymphocytes is, however, markedly different. Patients are typically elderly with a high white cell count, marked splenomegaly and heavy marrow infiltration. Marker analysis is distinct from typical CLL and extranodal features at presentation are atypical of SLVL and nodal MZL. FISH results in two cases were also atypical for CLL. The clinical behaviour is distinct with resistance to alkylating agents but sensitivity to purine analogues. We believe that these unique cases represent an as yet undescribed leukaemic variant of monocytoid MZL probably currently classed and treated as atypical CLL.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2698-2698
Author(s):  
Nerea Martinez ◽  
Ignacio Varela ◽  
Jose P. Vaque ◽  
Sophia Derdak ◽  
Sergi Beltran ◽  
...  

Abstract Abstract 2698 Background: Splenic marginal zone lymphoma (SMZL) is a small B cell neoplasm whose molecular pathogenesis is still unknown. It has a relatively indolent course, but a fraction of the cases may show an aggressive behavior. The lack of comprehensive molecular analysis for SMZL precludes the development of targeted therapy. Here we studied the mutational status of 6 SMZL samples using Whole Exome Next Generation Sequencing. Methods: Genomic DNA was extracted from splenic tumor or peripheral blood samples and oral mucosa as the corresponding non-tumor control. Whole exome sequencing was performed at CNAG (Barcelona, Spain) following standard protocols for high-throughput paired-end sequencing on the Illumina HiSeq2000 instruments (Illumina Inc., San Diego, CA). The variant calling was performed using an in house written software calling potential mutations showing a minimum independent multi-aligner evidence. Results: We performed paired-end-76pb whole exome sequencing on 6 SMZL samples and the corresponding normal counterpart. Three of the samples corresponded to CD19 isolated cells from peripheral blood, while other three corresponded to spleen freshly frozen tissue. The mean coverage obtained was 104.07 (82.46–119.59) with a mean of 91.41% (90.41–93.73) of bases with at least 15× coverage. After filtering, 237 substitutions and 21 indels where obtained. No recurrent variation was found. Six of the variations found here were already described in other malignancies. Variations were classified into silent (75), missense (147), nonsense (8), and essential splice (5), according to their potential functional effect, and into tolerated (54) and deleterious (76) according to the “variant effect predictor” tool of Ensembl Genome Browser. Whole exome sequencing permitted us to identify variations in several genes of TLR/NFkB pathway (Myd88, Peli3), BCR (Myd88, Arid3A) or signal transduction (ARHGAP32), essential pathways for B-cell differentiation. These variations and other involving selected genes, such as the Bcl6 repressor BCOR, were validated by capillary sequencing. These results were confirmed and expanded in a second series of 10 new cases by exome sequencing. Conclusions: SMZL samples contain somatic mutation involving genes regulating BCR signaling, TLR/NFKB pathways and chromatin remodeling. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2001 ◽  
Vol 98 (5) ◽  
pp. 1298-1301 ◽  
Author(s):  
Alun V. Evans ◽  
Blair P. Wood ◽  
Julia J. Scarisbrick ◽  
Elizabeth A. Fraser-Andrews ◽  
Sue Chinn ◽  
...  

Data were analyzed from 23 patients with Sézary syndrome (defined by erythroderma, more than 10% circulating atypical mononuclear cells, and peripheral blood T-cell clone) undergoing monthly extracorporeal photopheresis as the sole therapy for up to 1 year. The cohort showed a significant reduction of skin scores during treatment (P = .001). Thirteen patients (57%) achieved a reduction in skin score greater than 25% from baseline at 3, 6, 9, or 12 months (responders). Reduction in skin score correlated with reduction in the Sézary cell count as a percentage of total white cell count (P = .03). Responders and nonresponders were compared. None of the measured parameters was significantly different between the 2 groups. It was assessed whether any of the baseline parameters predicted outcome. A higher baseline lymphocyte count was significantly associated with a decrease in skin score at 6 months (P < .05). A higher baseline Sézary cell count as a percentage of total white cell count predicted a subject was more likely to be a responder after 6 months of treatment (P = .021). No other parameters predicted responder status. These data show that the modest falls in CD4, CD8, and Sézary cell counts were seen in all patients and might have resulted from lymphocyte apoptosis. This mechanism could explain the more favorable response seen in patients with higher percentages of Sézary cells in the peripheral blood. Alternatively, minimum tumor burden might be required for the induction of a cytotoxic response. Analysis of tumor-specific cytotoxic T cells is needed to investigate these possibilities further.


2011 ◽  
Vol 31 (3) ◽  
pp. 242-244 ◽  
Author(s):  
A. C. Herlihy ◽  
R. E. Kelly ◽  
J. L. Hogan ◽  
N. O'Connor ◽  
N. Farah ◽  
...  

1973 ◽  
Vol 30 (01) ◽  
pp. 036-046 ◽  
Author(s):  
D.C Banks ◽  
J.R.A Mitchell

SummaryWhen heparinised blood is rotated in a glass flask at 37°C. the white cell count falls and it has been shown that this is due to the adherence and aggregation of polymorphonuclear white cells on the wall of the flask. The masses formed bear a close structural resemblance to thrombi and the mechanisms involved in white cell loss during rotation may therefore increase our knowledge of the thrombotic process.


1979 ◽  
Author(s):  
M Drummond ◽  
G Lowe ◽  
J Belch ◽  
C Forbes ◽  
J Barbenel

We investigated the reproducibility and validity of a simple method of measuring red cell deformability (filtration of whole blood through 5 µ sieves) and its relationship to haematocrit, blood viscosity, fibrinogen, white cell count, sex and smoking. The mean coefficient of variation in normals was 3. 7%. Tanned red cells showed marked loss of deformability. Blood filtration rate correlated with haematocrit (r = 0. 99 on dilution of samples, r = 0. 7 in 120 normals and patients). After correction for haematocrit, deformability correlated with high shear viscosity, but not low shear viscosity, fibrinogen or white cell count. In 60 normals there was no significant difference between males and females, or smokers and non-smokers, but in 11 smokers there was an acute fall in deformability after smoking 3 cigarettes (p<0. 05). Reduced deformability was found in acute myocardial infarction (n = 15, p<0. 01) and chronic peripheral arterial disease (n = 15, p<0. 01). The technique is reproducible, detects rigid cells and appears useful in the study of vascular disease.


Sign in / Sign up

Export Citation Format

Share Document