Blood B-cell counts Individuals with<unk>  usually present with unexplained increases in blood lymphocyte counts (i.e.<unk> . The most common causes for<unk>  are viral infections, autoimmune diseases (particularly connective tissue diseases), hypersensitivity reactions, acute stress reactions, and prior splenectomy. Unlike many individuals with<unk>  due to the latter disorders, individuals with<unk>  are asymptomatic, may have a family history of CLL/SLL, are usually >40 years old, and may have a history of serious infections (high-count<unk>  is ~3-fold more likely than age-matched healthy controls to have a history of serious infections and infection-related hospitalizations). The diagnosis of<unk>  in these patients depends on finding 0.5-5x109<unk>  B cells that express the makers characteristic of CLL/SLL MLB, atypical CLL/SLL MLB, non-CLL/SLL MLB, or MLB-MZ. However, individuals with CBL-MZ commonly present with B-cell blood counts that are extremely high (>4.0x109; range 3.0x109/L to 37.1x109/L); and may have an IgM<unk>  gammopathy. Bone marrow involvement Most individuals with<unk>  have at presentation an abnormal infiltrate of<unk>  B-cells in their bone marrow as determined by biopsy. These B cells represent a median value of ~20% of all nucleated cells in the marrow. Regardless of the percentage of these cells, the presence of<unk>  B cells in bone marrow does not appear to influence the malignant progression of<unk>  and is not part of the criteria used to diagnose the disorder. Nodal<unk> <unk>  patients may present with asymptomatic lymphadenopathy (i.e. lymph nodes that are enlarged or abnormal in consistency). In one study, ~42% of<unk>  patients had enlarged lymph nodes as detected by CT scans. Nonetheless, these patients' rate of progression to malignant disease does not differ from that for<unk>  patients that had normal CT scans. However, patients who have grossly enlarged (i.e. >1.5 centimeters) (cm) lymph nodes on physical examination do have a greater risk of progression. It has been recommended that patients with ≥1 lymph node larger than 1.5 cm be diagnosed as having Cll/SLL, that patients with lymph nodes ≤1.5 cm in size be diagnoses as having normal<unk> , and that CT scans should not be used in diagnosing or staging<unk> .<unk>  with autoimmune cytopenia Rare patients with<unk>  may present with the autoimmune disease-induced cytopenias of hemolytic anemia (reduced circulating red blood cell numbers) or thrombocytopenic purpura (reduced circulating platelet numbers). In the past, cases of CLL/SLL<unk>  associated with an autoimmune disease were diagnosed as CLL/SLL. However, patients with these autoimmune disorders who have very small B cell clones either never develop a lymphocyte malignancy or, rarely, do so and only after many years. Consequently, it is now widely recognized that such cases, when associated with very small numbers of<unk>  B-cells, are best diagnosed as CLL/SLL<unk>  with autoimmune cytopenia rather than CLL/SLL. Tissue-based<unk><unk>  CLL/SLL phenotype B cells have been found using sensitive flow cytometry methods in various tissues. They have been identified as infiltrates in 1.9% of liver biopsies and 0.4% of prostate tissues obtained at prostatectomy. While the significance of these lesions is unknown, the presence of extensive infiltrations that replace normal tissue is more consistent with a diagnose of CLL/SLL than CLL/SLL<unk> . Differential diagnosis The key factor that distinguishes low-count CLL/SLL-MLB, high-count CLL/SLL-MLB, and CLL/SLL is the number of circulating<unk>  B cells, as described above. However, the other MLB phenotypes may progress to and/or be mimicked by various<unk>  B-cell lymphocyte malignancies. The key cell markers and other points that help distinguish the following<unk>  phenotypes from these malignancies include the following (refer to Table for comparisons to non-malignant predecessor cells): * Atypical CLL/SLL-MBL * Mantle cell lymphoma: The<unk>  B-cells in this aggressive lymphoma are CD5+ in most cases, CD10−, CD23−, CD43+, CD103−, complete Ig+, and express cyclin D1; these cells have translocations between chromosomes 11 and 14 in >95% of cases and in many cases overexpress the SOX11 transcription factor gene. Testing for the chromosome 11, 14 translocation has been recommended for all cases of atypical and non-CLL/SLL<unk> . * Follicular lymphoma: The<unk>  B-cells in this indolent lymphoma are CD5−, CD10+/−, CD19+, CD20+, CD23+/−, CD103−, CD200− and complete Ig+. These cells often exhibit translocations between chromosomes 14 and 18. * non-CLL/SLL-ML * Splenic marginal zone lymphoma: The<unk>  B-cells in this indolent lymphoma are CD5+/−, CD10−, CD19+, CD23−, CD43−, CD103−, and do not express cyclin D1. These cells may bear deletion in the "q" arm of chromosome 7 (30% of cases), and mutations in NOTCH2 (10-25% of cases), KLF2 (10-40% of cases), and, rarely, MYD88 genes. The<unk>  cells are also CD200− and are complete Ig+. Patients with this lymphoma commonly have an enlarged spleen. * Splenic B-cell lymphoma/leukemia unclassifiable: The rare reports on this lymphoma find the<unk>  B cells to be CD19+, CD20+ (bright, CD23+, CD11+, CD25−, CD103−, CD72+, and annexin A1−. These cells, similar to the<unk>  cells in Hairy cell leukemia, may have the V600E mutation in the BRAF gene. Patients with this lymphoma commonly have enlarged spleens. *<unk> -MZ * Splenic marginal zone lymphoma and splenic B-cell lymphoma/leukemia: see above descriptions. * Waldenström's macroglobulinemia: The<unk>  B-cells in this indolent lymphoma are CD5− (in most cases), CD10−, CD19+, CD23−, CD43−/+, CD103−, cyclin D1+, Cd200−, and globulin + (dim). The cells contain the L265P mutation in the MYD88 (>90% of cases) and a mutation in the CXCR4 gene (30% of cases). Patients with this lymphoma commonly have an IgM gammaopathy, i.e. high blood levels of an IgM<unk>  protein. * Hairy cell leukemia: The<unk>  B-cells in this usually indolent CLL/SLL-like leukemia have a distinctive morphology and are CD5−, CD10−, CD19+, CD20+ (bright), CD23−, CD103+, CD200+, and complete Ig+. In situ lymphoid neoplasia In situ lymphoid neoplasia (ISLN), a lymphocyte disorder newly categorized by the World Health Organization (2016,) has several features in common with MLB. Like<unk> , it is an asymptomatic, premalignant disorder of B-cells that is associated with the circulation of these cells and may progress to follicular lymphoma, mantle cell lymphoma, or CLL/SLL. ISLN differs from<unk>  in that its neoplastic B-cells accumulate in the follicles of lymphoid tissue, usually circulate in very low numbers, and bear distinctive genetic abnormalities that differ from those in<unk> . ISNL is diagnosed based on, and requiring, the finding of these neoplastic B-cells in lymphoid follicles.
Monoclonal B-cell lymphocytosis
Persistent polyclonal B-cell lymphocytosis
Abscess of thymus
Idiopathic CD4+ lymphocytopenia
Cutaneous lymphoid hyperplasia
Persistent generalized lymphadenopathy
Thymic hypoplasia
Lymphoid neoplasms with plasmablastic differentiation