Chronic Lymphocytic Leukemia with Bi-Nucleated Lymphocytes

Introduction: B-cell chronic lymphocytic leukemia is one of the common lymphoproliferative disorders in the adult patient population. It is very uncommon to find bi-nucleated lymphocytes as a morphological feature in this disorder. Our patient was diagnosed with CLL and was found to have bi-nucleated lymphocytes in the peripheral smear. The mechanism behind this type of morphological feature of lymphocytes is unknown in CLL, and whether it has prognostic value on disease outcome is undetermined.

Case Description: 62 y/o man was referred to hematology oncology after diagnosis of small cell lymphocytic leukemia was made s/p a right inguinal lymph node biopsy. His CBC revealed a wbc count of 14,000, Rbc count of 4,360, Absolute lymphocyte count of 11,500 and Platelet count of 125,000. The patient did not have any B-symptoms. On physical exam, a pertinent finding was palpable right axillary adenopathy. The CT of abdomen /pelvic to evaluate these findings. This revealed extensive axillary, abdominal/pelvic lymphadenopathy, hepatosplenomegaly and cardio phrenic lymphadenopathy.

The patient had a biopsy of the right inguinal lymph node as well as bone marrow biopsy. Biopsy results showed small lymphocytic cells, some of which show occasional large nucleoli were consistent with small lymphocytic lymphoma/chronic lymphocytic leukemia, and morphologic characteristics of the lymphocytes showed bi-nucleated lymphocytes in peripheral blood smear (figure A). Flow cytometric analysis confirmed a lymphocytic population with lambda light chain restriction, expressing CD5, CD19, CD20, and CD23 consistent with chronic lymphocytic leukemia/small lymphocytic lymphoma. Bone marrow biopsy showed a hypercellular marrow with 75 % cellularity mainly composed of mature lymphocytes with scattered macrophages and eosinophils, Flow cytometric analysis (Clarient FI11-041053) of the bone marrow is interpreted as chronic lymphocytic leukemia/small cell lymphoma with the abnormal B cells representing 56% of the viable white cells. FISH study showed deletion of the ATM gene (11q22-23), D13S319 (13q14) and TP53 (p53) were observed in 29%, 71% and 35.5% of the cells analyzed, respectively. A subset of cells with the 13q deletion (20.5% of the total cells) showed homozygous deletion of D13S319 (13q14). ATM deletion is associated with progressive disease and poor prognosis in cases of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).He did not have any other previous history of malignancy or hematologic disorder.

Discussion:

B-cell chronic lymphocytic leukemia is one of the common lymphoproliferative disorders in the adult patient population. To make a diagnosis requires absolute lymphocyte count >4x10 9 and lymphoid cell morphology. In CLL, leukemic cells are small and mature appearing lymphocytes, which have regular nuclear and cytoplasmic outlines and scant weakly basophilic cytoplasm. Surface markers that define a CLL cell are proteins such as antibody light chains (kappa or lambda) and CD proteins (CD5, CD19, CD20, and CD23). In our patient absolute lymphocyte count was 11.5x10⁹ and lymphocytic population showed surface marker lambda light chain and CD proteins CD5, CD19, CD20 and CD23 which was consistent with CLL/SLL on inguinal lymph node biopsy, but morphology of lymphocytes was small and mature bi-nucleated lymphocytes, which is very uncommon. Although bi-nucleated lymphocytes are described in a disorder "Polyclonal chronic B-cell lymphocytosis with bi-nucleated lymphocytes". Detection of an extra chromosome for the long arm of chromosome 3 +i(3)(q10) has been considered a specific marker of Polyclonal B-cell lymphocytosis with binucleated lymphocytes (PPBL),which was not present in our case. One case study by Amouroux et al, included four patients with B-cell CLL who were found to have bi-nucleated lymphocytes. Disease course was stable in one patient, one patient had an indolent course and only one required treatment due to rapid doubling time of lymphocytes. Our patient initiated chemotherapy with Rituxan and Fludara, as he had progressive disease with hepatosplenomegaly, lymph nodes and bone marrow involvement.

Conclusion:

Bi -nucleated lymphocytes in B-cell CLL are very rare. Explanations as to the etiology of this morphological feature in B-cell CLL is unknown. There is no sufficient evidence that bi-nucleated lymphocytes in CLL has any impact on disease progression.