Not All Lymphocytosis Is Chronic Lymphocytic Leukemia (CLL): A Retrospective Review of Patients Referred to an Academic Hematology Oncology Center for CLL
Authors: Kiamos Amy , Boldig Kimberly , Quan Walter JR 
Published: December 2023

Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults, especially in elderly patients. Most patients with CLL are asymptomatic at presentation and have routine blood work that prompts further investigation. In patients with CLL, their complete blood cell count with differential typically demonstrates lymphocytosis due to the increased number of malignant B-lymphocytes. Although lymphocytosis can be suggestive of CLL, diagnostic workup can sometimes reveal an alternative diagnosis. Here we describe a retrospective review of 36 patients referred to our hematology oncology clinic for the suspected diagnosis of CLL.
Out of the 36 patients referred for CLL, 8 patients (22%) had diagnostic workup confirming an alternative diagnosis including non-Hodgkin lymphoma (NHL) (5 patients), hairy cell leukemia (1 patient), and monoclonal B-cell lymphocytosis (2 patients). Only 28/36 (78%) of total patients had flow cytometry confirming the diagnosis of CLL. Out of the 36 total patients, 34 patients had lab work revealing lymphocytosis (absolute lymphocyte count greater or equal to 5.0 10 3/mL) prompting referral. At presentation, total patients (34/36) with lymphocytosis had an absolute lymphocyte count range of 5-593.0 (10 3/mL), median of 17.6 (10 3/mL), and average of 50.8 (10 3/mL). 27/34 (79%) of patients with lymphocytosis were diagnosed with CLL, while 7/34 (21%) of patients with lymphocytosis initially suggestive of CLL were diagnosed with alternative diagnoses (follicular lymphoma (1), marginal zone lymphoma (2), mantle lymphoma (1), hairy cell leukemia (1), and monoclonal B-cell lymphocytosis (2)).
The patients with lymphocytosis not diagnosed with CLL (7/34 patients) had an absolute lymphocyte count range of 5-105.6 (10 3/mL), median of 18.27 (10 3/mL), and average of 45.2 (10 3/mL). Their average age at presentation was 63 years old (range of 53-80). Most common symptoms at presentation were asymptomatic (3), B-symptoms plus lymphadenopathy (2), lymphadenopathy (1), and gastrointestinal symptoms (1). The asymptomatic patients were monoclonal B-cell lymphocytosis (2) and mantle lymphoma (1). Hairy cell leukemia, marginal zone lymphoma, and follicular lymphoma had significantly elevated absolute lymphocyte count (86.8, 105.6, 89.45 (10 3/mL) respectively) and associated anemia. Only one patient referred for CLL was diagnosed with follicular lymphoma had anemia and thrombocytopenia without lymphocytosis.
The patients with lymphocytosis confirmed to have CLL (27/34 patients) had an absolute lymphocyte count range of 5-593 (10 3/mL), median of 17.6 (10 3/mL), and average of 50.8 (10 3/mL). Their average age at presentation was 70 years old (range 54-93). Most common symptoms at presentation were asymptomatic (16), B-symptoms plus lymphadenopathy (5), lymphadenopathy only (2), B-symptoms only (2), and neck/back pain (2). 59% of patients were asymptomatic with abnormal lab work including lymphocytosis only (14), anemia (1), and abnormal M-spike on serum protein electrophoresis (1).
We wish to emphasize the role of flow cytometry and its value in confirming diagnosis of CLL. Even if clinical suspicion for CLL is high, it is important to not solely rely on complete blood cell count and peripheral lymphocyte count. NHL, hairy cell leukemia, and monoclonal B-cell lymphocytosis can have similar lab work and initial presenting symptoms to patients with CLL. A few patients in this review were receiving chemotherapy for CLL initially and were later found to have a different diagnosis. It is important to keep clinical suspicion high for alternative diagnoses for lymphocytosis to guide appropriate management.