Department of Clinical Pathology, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Haematologica. 2011 Aug;96(8):1121-7. doi: 10.3324/haematol.2010.036277. Epub 2011 Apr 20.
Cases of mantle cell lymphoma with indolent behavior have been reported, but are poorly identified by current clinical risk models. Early studies found peripheral blood involvement to be an adverse prognostic factor; however, cases of a seemingly indolent variant of mantle cell lymphoma, characterized by peripheral blood involvement and minimal nodal disease, have been incompletely described, particularly with regard to bone marrow findings. We report a series of leukemic phase mantle cell lymphomas with a non-progressive or slowly progressive course.
Cases presenting with mantle cell lymphoma limited to the peripheral blood/bone marrow from 2000-2010 were identified. Diagnoses were established by morphology, flow cytometric analysis and requisite evidence of IGH-CCND1@ by fluorescence in-situ hybridization or t(11;14)(q13;q32) by cytogenetics. Patients with lymphadenopathy, splenomegaly and gastrointestinal symptomatology were excluded.
Patients (n=8, median age 60.5 years) were asymptomatic with mild lymphocytosis (8.7×10(9)/L; range, 4.5-14.2×10(9)/L) and cytology typical of mantle cell lymphoma. Flow cytometric analysis showed that all expressed CD5, CD19, CD20, variable CD23, and a striking kappa immunoglobulin light chain restriction (7/8 cases). Bone marrow biopsy at diagnosis showed interstitial single or small lymphoid aggregates with similar patterns of CD20 and cyclin D1 immunostaining which were not readily discernable by hematoxylin and eosin stain. SOX11 was negative (4/5) or only weakly expressed (1/5). The median follow-up was 27 months (range, 5-109 months) and all patients, but one, are alive with no clinical evidence of disease. The prevalence of indolent mantle cell lymphoma presenting only with lymphocytosis, among all mantle cell lymphomas diagnosed during the same period, was 3%.
Leukemic mantle cell lymphoma limited to blood and bone marrow is an indolent variant characterized by mild-moderate lymphocytosis, interstitial low-level bone marrow involvement, simple karyotype, kappa light chain expression, cyclin D1 expression with lack of SOX11, and slow or absent clinical progression. Some cases may represent a mantle cell lymphoma counterpart to chronic lymphocytic leukemia - phenotype monoclonal B-cell lymphocytosis. Recognition of this variant could inform treatment decisions and possibly avoid unnecessary treatment.
目前的临床风险模型对惰性表现的套细胞淋巴瘤病例识别能力较差，但已有报道称存在此类病例。早期研究发现外周血受累是一个不利的预后因素；然而，外周血受累和少量淋巴结疾病为特征的、看似惰性的套细胞淋巴瘤变异型的病例描述并不完全，尤其是骨髓发现方面。我们报告了一系列白血病期套细胞淋巴瘤，这些病例表现为非进展性或缓慢进展性病程。
从 2000 年至 2010 年期间，我们确定了仅表现为外周血/骨髓受累的套细胞淋巴瘤病例。通过形态学、流式细胞分析以及荧光原位杂交检测到 IGH-CCND1@或通过细胞遗传学检测到 t(11;14)(q13;q32)，从而确立诊断。排除有淋巴结肿大、脾肿大和胃肠道症状的患者。
患者（n=8，中位年龄 60.5 岁）无症状，仅有轻度淋巴细胞增多症（8.7×10(9)/L；范围，4.5-14.2×10(9)/L）和典型的套细胞淋巴瘤细胞学特征。流式细胞分析显示，所有患者均表达 CD5、CD19、CD20、可变 CD23，并表现出显著的κ轻链免疫球蛋白限制（7/8 例）。在诊断时的骨髓活检中，可见间质内单个或小的淋巴细胞聚集，CD20 和 cyclin D1 免疫染色模式相似，苏木精和伊红染色不易辨认。SOX11 阴性（4/5）或仅弱阳性（1/5）。中位随访时间为 27 个月（范围，5-109 个月），除 1 例患者外，所有患者均存活且无疾病临床证据。在同一时期诊断的所有套细胞淋巴瘤中，仅表现为淋巴细胞增多症的惰性套细胞淋巴瘤的患病率为 3%。
局限于血液和骨髓的白血病性套细胞淋巴瘤是一种惰性变异型，其特征为轻度至中度淋巴细胞增多症、间质低度骨髓受累、简单核型、κ 轻链表达、cyclin D1 表达但缺乏 SOX11，以及缓慢或无临床进展。某些病例可能代表慢性淋巴细胞白血病-表型单克隆 B 细胞淋巴细胞增多症的套细胞淋巴瘤对应物。认识到这种变异型有助于做出治疗决策，并且可能避免不必要的治疗。
