Department of Pathology, University Hospitals Cleveland Medical Center/Cast Western Reserve University School of Medicine, Cleveland, OH, 44106, USA.
Department of Pathology, University Hospitals Cleveland Medical Center/Cast Western Reserve University School of Medicine, Cleveland, OH, 44106, USA.
Hum Pathol. 2022 Jul;125:108-116. doi: 10.1016/j.humpath.2022.04.010. Epub 2022 Apr 25.
Monoclonal B-cell lymphocytosis is a clonal B-cell population in the peripheral blood (PB) of <5x10ˆ9/L without extramedullary (EM) disease, often with a chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) phenotype. The degree of bone marrow (BM) involvement is not currently a part of the diagnostic criteria for MBL or CLL/SLL, but CLL-type MBLs in BM can be seen in patients lacking PB lymphocytosis. Data are limited on the outcome of such cases. We assessed the clinicopathologic characteristics of isolated BM CLL-type MBL in patients who did not meet criteria for CLL/SLL. We evaluated BMs from 2006 to 2018 with CLL-like clonal B-cell populations in patients with a PB absolute lymphocyte count or monoclonal B-cell count of <5 × 10/L and without definite evidence of EM disease. We investigated the extent and pattern of marrow involvement, PB counts, flow cytometric data, genetics, concurrent hematopoietic diseases, and outcomes including progression and treatment. Thirty cases with BM MBL but <5x10E9/L PB monoclonal B cells and no EM disease were identified. Thirteen of 30 had additional hematopoietic neoplasms. The mean patient age was 74.1 years (median: 77 years, range: 43-91 years). No patients had lymphadenopathy (LAD) or splenomegaly by physical examination. By imaging, nine of 18 had LAD (8/9 < 1.5 cm) and four of 18 had splenomegaly but with other attributable etiologies. Mean PB absolute lymphocyte count (ALC) was 1.8×10E9/L (range: 0.5-5.0×10E9/L). Twenty-four of 30 (80%) had low-level (<20%) BM involvement by MBL, and among these, none with available follow-up data progressed to diagnostic CLL/SLL. Six of 30 (20%) had >20% marrow involvement by MBL. Four of 6 were treated for CLL/SLL due to cytopenias, despite not meeting diagnostic criteria, and all 4 were CD38 or ZAP70 positive and had cytogenetic abnormalities, including trisomy 12. One of 6 developed overt CLL/SLL 3 years later and had cytogenetic abnormalities at the time of MBL diagnosis. One of 6 was monitored without treatment but had no cytogenetic abnormalities.Isolated BM CLL-type MBL represents a diagnostic gray area, and this study highlights the range of clinical outcomes. All cases with <20% BM involvement did not require CLL-specific treatment or progress to CLL/SLL. In the 4 cases where treatment was initiated due to cytopenias, patients had ≥20% BM involvement, CD38 or ZAP70 expression, and cytogenetic abnormalities but lacked a PB ALC of ≥5x10E9/L or LAD ≥1.5 cm, suggesting that not all patients with clinically significant disease will meet criteria for CLL/SLL. The results also show that concurrent hematopoietic disorders can complicate the diagnosis, as the disease course or treatment may result in leukopenia, precluding PB absolute lymphocytosis. Though larger studies are needed, the degree of BM involvement, in conjunction with flow cytometric prognostic markers, and cytogenetic abnormalities may be a useful addition to the current diagnostic criteria for CLL/SLL which only considers a PB numerical cutoff and EM involvement.
单克隆 B 细胞淋巴细胞增多症是外周血（PB）中 <5x10ˆ9/L 的克隆性 B 细胞群体，无骨髓外（EM）疾病，常伴有慢性淋巴细胞白血病（CLL）/小淋巴细胞淋巴瘤（SLL）表型。骨髓（BM）受累程度目前不是 MBL 或 CLL/SLL 诊断标准的一部分，但在缺乏 PB 淋巴细胞增多症的患者中可以看到 CLL 型 MBL 累及 BM。关于这种情况的结果数据有限。我们评估了不符合 CLL/SLL 标准的患者中孤立性 BM CLL 型 MBL 的临床病理特征。我们评估了 2006 年至 2018 年间 PB 绝对淋巴细胞计数或单克隆 B 细胞计数 <5x10/L 且无明确 EM 疾病证据的患者的 BM，其中存在类似 CLL 的克隆性 B 细胞群体。我们研究了骨髓受累的程度和模式、PB 计数、流式细胞术数据、遗传学、同时存在的造血疾病以及包括进展和治疗在内的结局。确定了 30 例 BM MBL 但 <5x10E9/L PB 单克隆 B 细胞且无 EM 疾病的病例。30 例中有 13 例存在其他造血肿瘤。患者的平均年龄为 74.1 岁（中位数：77 岁，范围：43-91 岁）。体检无淋巴结病（LAD）或脾肿大。通过影像学检查，18 例中有 9 例（8/9 <1.5cm）有 LAD，18 例中有 4 例有脾肿大，但有其他可归因的病因。平均 PB 绝对淋巴细胞计数（ALC）为 1.8x10E9/L（范围：0.5-5.0x10E9/L）。30 例中有 24 例（80%）有低水平（<20%）的 MBL 累及 BM，其中无进展为诊断 CLL/SLL 的可用随访数据。30 例中有 6 例（20%）有 >20%的骨髓受累。6 例中有 4 例因血细胞减少而接受 CLL/SLL 治疗，尽管不符合诊断标准，但这 4 例均为 CD38 或 ZAP70 阳性且存在细胞遗传学异常，包括三体 12。6 例中有 1 例在 3 年后出现明显的 CLL/SLL，且在 MBL 诊断时存在细胞遗传学异常。6 例中有 1 例未接受治疗但无细胞遗传学异常而进行监测。孤立性 BM CLL 型 MBL 代表一个诊断的灰色区域，本研究突出了其广泛的临床结局。所有 <20% BM 受累的病例均无需进行 CLL 特异性治疗或进展为 CLL/SLL。在 4 例因血细胞减少而开始治疗的病例中，患者存在≥20%的 BM 受累、CD38 或 ZAP70 表达和细胞遗传学异常，但缺乏 PB ALC ≥5x10E9/L 或 LAD ≥1.5cm，表明并非所有具有临床意义的疾病的患者都符合 CLL/SLL 的标准。结果还表明，同时存在的造血疾病可能会使诊断复杂化，因为疾病过程或治疗可能导致白细胞减少，从而排除 PB 绝对淋巴细胞增多症。虽然需要进行更大的研究，但 BM 受累程度、流式细胞术预后标志物和细胞遗传学异常可能是目前 CLL/SLL 诊断标准的有用补充，目前的诊断标准仅考虑 PB 数值截断值和 EM 受累。
