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Chronic Lymphocytic Leukemia: Thrombocytopenia

Medical University of South Carolina

View larger version (163K): [in this window] [in a new window]   Figure 1. Low-power view of peripheral smear showing in a patient with CLL showing small lymphocytes and numerous "smudge" or "basket" cells (arrows). Platelets are scarce.

View larger version (153K): [in this window] [in a new window]   Figure 2. Higher power view of the same peripheral smear showing small lymphocytes and "smudge" or "basket" cells (arrows). Note also the paucity of platelets; platelet count was 52,000/uL.

View larger version (140K): [in this window] [in a new window]   Figure 3. Peripheral smear showing prolymphocytes (arrows) and a small lymphocyte. The prolymphocytes have abundant cytoplasm and large nucleolus. In CLL, prolymphocytes may constitute up to 14% of the lymphocyte population.

View larger version (46K): [in this window] [in a new window]   Figure 4. Flow cytometric analysis of cells obtained on bone marrow aspiration. Panel A: Cells marked for both CD 19 and CD 5. Panel B: Cells are positive for CD 19 but are negative for CD 10. This immunophenotype can be seen in both chronic lymphocytic leukemia and mantle cell lymphoma.

View larger version (92K): [in this window] [in a new window]   Figure 5. Flow cytometric analysis of cells obtained on bone marrow aspiration were CD 20 and CD 23 positive (quadrant 2) consistent with a diagnosis of CLL.

View larger version (34K): [in this window] [in a new window]   Figure 6. Flow cytometric analysis for immunoglobulin light chain monoclonality of cells obtained on bone marrow aspiration. Panel A: Circled area represents selection of CD 19 positive cells. Panel B: These cells are also dimly positive for kappa light chain, but are negative for lambda light chain as shown in Panel C. This study confirms that the B lymphoclytes are a clonal population. Dim light chain staining is characteristic of CLL.

View larger version (136K): [in this window] [in a new window]   Figure 7. Bone marrow aspirate with a single megakaryocyte and numerous small lymphocytes. Thrombocytopenia in CLL can result from decreased megakaryopoiesis due to marrow replacement.

View larger version (134K): [in this window] [in a new window]   Figure 8. Bone marrow aspirate showing numerous prolymphocytes. In a patient with CLL, this may represent a transformation to a more aggressive disease. Thick arrow shows a small lymphocyte.

View larger version (147K): [in this window] [in a new window]   Figure 9. Bone marrow biopsy showing a nodular pattern of infiltration of small lymphocytes at the top and an interstitial pattern below.

View larger version (148K): [in this window] [in a new window]   Figure 10. Immunohistochemicalstain using L-26 (CD 20) antibody confirming that these cells are B lymphocytes.

View larger version (143K): [in this window] [in a new window]   Figure 11. Bone marrow biopsy showing immunohistochemicalstain using CD 5 antibody of nodular infiltrate in a patient with CLL.

View larger version (149K): [in this window] [in a new window]   Figure 12. Bone marrow biopsy showing diffuse replacement of the marrow by CLL. Normal hematopoietic elements can not be recognized.

View larger version (188K): [in this window] [in a new window]   Figure 13. Marrow biopsy showing diffuse marrow replacement by small lymphocytes of CLL. The lighter staining area (arrow) has a pseudofollicle appearance due to numerous prolymphocytes.

View larger version (162K): [in this window] [in a new window]   Figure 14. Bone marrow biopsy in a patient with CLL showing an interstitial pattern of involvement. Normal marrow elements are present.

View larger version (135K): [in this window] [in a new window]   Figure 15. Bone marrow biopsy illustrating megakaryocytic hyperplasia. Megakaryocytic hyperplasia can be seen in immune-mediated thrombocytopenia associated with CLL.

	Clinical Summary

TOP Clinical Summary Diagnosis Discussion Differential Diagnosis

Multiple small cervical nodes are palpable; axillary nodes 1-2 cm are present bilaterally; inguinal adenopathy is also present. The liver is not enlarged; however, the splenic tip is palpable. Purpuric lesions are evident on the lower extremities.

Additional lab: SPEP - albumin 3.4g/dL and globulins 2.5 g/dL. CT scan of abdomen -retroperitoneal adenopathy;splenomegaly.

Sex
Male

Age
59

Ethnicity
White

	Diagnosis

TOP Clinical Summary Diagnosis Discussion Differential Diagnosis

 
Immune-mediated thrombocytopenia, Thrombocytopenia due to marrow replacement, Thrombocytopenia associated with hypersplenism

	Discussion

TOP Clinical Summary Diagnosis Discussion Differential Diagnosis

 
Chronic lymphocytic leukemia (CLL) is a neoplasm of long- lived small B cells that express high levels of anti-apoptosis protein BCL-2. The National Cancer Institute (NCI)-sponsored workshop on CLL requires for diagnosis a lymphocytosis of more than 5000 cells/uL, the cells immunophenotypically expressing pan B markers (CD 19, 20, 23), and co-expressing CD5 and having low intensity light chain restricted surface immunoglobulin. Bone marrow lymphocytosis is always present. The nodal counterpart of this disorder is small lymphocytic lymphoma (SLL). Clinically, most patients are over 60 years old, but it has been  reported rarely in individuals under 25 years old. Although most patients are asymptomatic at the time of diagnosis, weight loss, recurrent infection, anemia, and thrombocytopenia may be part of the presentation. Lymphadenopathy is found in 80% of patients and can be minimal or massive. Splenomegaly is noted in 50% of patients. Bone marrow involvement can be interstitial (40%), nodular (10%), diffuse (25%), or a combination of these (25%). Hypogammaglobulinemia is common but 5% of patients will have an IgM paraprotien.

Approximately 80% of patients will have an abnormal karyotype using fluorescent in-situ hybridization (FISH), including trisomy 12, and del 13q14. Thrombocytopenia associated with CLL is common and is seen in 50% of patients at presentation and becomes higher as the disease progresses. It is usually due to bone marrow replacement by the malignant process and is an indication for therapy of the disease. In 2% of patients the thrombocytopenia is immune-mediated due to an autoantibody directed at platelet specific surface membrane antigens. This contrasts with the incidence of autoimmune hemolytic anemia which can be seen in 5% to 20% of these patients. Typical laboratory findings when an immune mechanism is present include large platelets on the peripheral smear, an elevated mean platelet volume (MPV), megakaryocytic hyperplasia on examination of the bone marrow, and a  positive platelet antibody test. Therapy in this case is similar to that used to treat autoimmune thrombocytopenia of any cause, which would include corticosteroids, IVIg, anti-Rh(D) and splenectomy.

	Differential Diagnosis

TOP Clinical Summary Diagnosis Discussion Differential Diagnosis

 
Immune-mediated thrombocytopenia, Thrombocytopenia due to marrow replacement, Thrombocytopenia associated with hypersplenism

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Related Image Bank Image Sets

Thrombotic Thrombocytopenic Purpura

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ASH Image Bank 2001 2001: 100174. [Full Text]

Related ASH-SAP Chapter:

This Article Figures Only Services Similar articles in this journal Alert me to new content in the Image Bank Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Lazarchick, J. Search for Related Content PubMed Articles by Lazarchick, J. Related Collections Platelet Disorders - Quantitative Abnormalities - Mucocutaneous hemorrhage Related ASH-SAP Chapter Related Image Bank Image Sets Social Bookmarking                   What's this?