血液学案例研究：在看似健康的年轻人中观察到的异常淋巴细胞

A healthy 30 year old woman visited her primary care physician concerned about a rash with questionable infection on her hands. The physician prescribed an antibiotic for infection and ordered a CBC. From the results below, it can be seen that the patient had a pancytopenia and a relative lymphocytosis.
一名健康的 30 岁女性去看了她的初级保健医生，担心她手上有可疑感染的皮疹。医生开了一种抗生素来治疗感染，并下令进行全血细胞计数。从下面的结果可以看出，患者有全血细胞减少症和相对淋巴细胞增多症。

A manual differential was performed on CellaVision and the presence of large, clefted lymphocytes with immature features was noted. A request for pathology review was sent to the pathologist. The pathologist’s review stated “ Atypical lymphocytosis, specimen to be submitted for flow cytometry. Report to follow. Occasional atypical lymphocytes with immature features also noted. Lymphocyte population is predominantly mature”
对 CellaVision 进行了手动鉴别，并注意到存在具有不成熟特征的大裂隙淋巴细胞。向病理学家发送了病理学审查请求。病理学家的评论指出“ 非典型淋巴细胞增多症，标本将提交流式细胞术。报告后续。还注意到偶尔具有不成熟特征的非典型淋巴细胞。淋巴细胞群以成熟为主”

The peripheral blood sample was sent out for immunophenotyping by flow cytometry and FISH studies. Flow cytology reported “precursor B-cell population expressing CD19, CD10, HLA-DR, and CD34 is identified. Percent of abnormal cells, 30%. These findings are consistent with precursor B-lymphoblastic leukemia.” While we tend to associate a leukemia diagnosis with a high white blood cell count, and the presence of blasts, this patient was unusual in that she did not have a high WBC or blasts seen on the peripheral smear. Pancytopenia in ALL has been noted in literature. A study of new onset pancytopenia in adults showed that the majority of cases were acute myeloid leukemia, but ALL and other lymphomas also caused pancytopenia 3 . Another study noted that “pancytopenia followed by a period of spontaneous recovery may precede the diagnosis of acute lymphoblastic leukemia.” 1 While the pathologist did not identify blasts on this differential, and cells were predominately mature, WBC was very low, and our analyzer did flag “?blasts/abnormal lymphs” and reflexed the manual differential.
外周血样本通过流式细胞术和FISH研究进行免疫表型分析。流式细胞学报告“鉴定出表达 CD19、CD10、HLA-DR 和 CD34 的前体 B 细胞群。异常细胞百分比，30%。这些发现与前体B淋巴细胞白血病一致。虽然我们倾向于将白血病诊断与高白细胞计数和原始细胞的存在联系起来，但该患者的不寻常之处在于她没有高白细胞或外周涂片上看到的原始细胞。文献中已注意到 ALL 中的全血细胞减少症。一项针对成人新发全血细胞减少症的研究表明，大多数病例是急性髓系白血病，但急性淋巴细胞白血病和其他淋巴瘤也会引起全血细胞减少症 3 。另一项研究指出，“全血细胞减少症和一段时间的自发恢复可能在急性淋巴细胞白血病的诊断之前出现。 1 虽然病理学家没有在这种分类检查中发现原始细胞，并且细胞主要是成熟的，但白细胞非常低，我们的分析仪确实标记了“原始细胞/异常淋巴”并反射了手动分类。

Leukemia is a broad term that includes a number of different chronic and acute diagnoses. Chronic and acute forms are further broken down into myeloid and lymphoid and then into subtypes. The French-American-British (FAB) classification of acute leukemias was devised in the 1970’s and 1980’s and was based on cytochemical staining and morphology of cells. These tests were performed manually and relied on what the cells look like under the microscope. The series of stains were used to differentiate myeloblasts from lymphoblasts. I’m old enough that I remember learning about these stains when they were being developed and thinking how amazing they were!
白血病是一个广义的术语，包括许多不同的慢性和急性诊断。慢性和急性形式进一步细分为骨髓和淋巴类型，然后细分为亚型。急性白血病的法美英 （FAB） 分类是在 1970 年代和 1980 年代设计的，基于细胞化学染色和细胞形态学。这些测试是手动进行的，并依赖于细胞在显微镜下的外观。该系列染色剂用于区分成髓细胞和淋巴母细胞。我已经足够大了，我记得在开发这些污渍时了解它们并认为它们是多么神奇！

We’ve come a long way since the early 1980’s! Although the FAB diagnostic criteria are not entirely forgotten, the World Health Association (WHO) classification, first published in 2001, has largely replaced the FAB classification. The newest guidelines for Acute Lymphoblastic Leukemias (ALL) were published by WHO in 2016. These new guidelines supplement morphology and cytochemical staining with newer testing which can now identify and distinguish B cell and T cell ALL. In making a diagnosis, peripheral blood and/or bone marrow aspirate samples are subject to flow cytometry immunophenotyping and chromosome testing such as cytogenics or fluorescence in situ hybridization(FISH). Molecular tests can also be done to look for specific gene changes in the leukemia cells. The WHO classification has become preferred because these new tests can give more information that is important for treatment. Prognosis for ALL depends on patient age, WBC counts at diagnosis and these specific test results which tell us which subtype of ALL is present. The presence and identification of chromosomal alterations is important for diagnosis and therapy decisions. Identifying chromosomal alterations can also lead to better risk classification which is significant because of the knowledge that, while rearrangements tend to have poorer outcomes, some rearrangements actually offer a better prognosis. With the future era of individualized, targeted therapy for leukemia, combining conventional cytogenics with molecular and FISH methods will greatly enhance the accuracy of information and provide patients with more specific and customized treatment options.
自 1980 年代初以来，我们已经走了很长一段路！尽管 FAB 诊断标准并未完全被遗忘，但 2001 年首次发布的世界卫生组织 （WHO） 分类已在很大程度上取代了 FAB 分类。世卫组织于2016年发布了最新的急性淋巴细胞白血病指南。这些新指南通过更新的测试补充了形态学和细胞化学染色，现在可以识别和区分 B 细胞和 T 细胞 ALL。在做出诊断时，外周血和/或骨髓抽吸物样本需要接受流式细胞术、免疫表型分析和染色体检测，例如细胞遗传学或荧光原位杂交 （FISH）。还可以进行分子测试以寻找白血病细胞中的特定基因变化。WHO分类已成为首选，因为这些新的测试可以提供更多对治疗很重要的信息。急性淋巴细胞白血病的预后取决于患者年龄、诊断时的白细胞计数以及这些特定的检查结果，这些结果告诉我们存在哪种急性淋巴细胞白血病亚型。染色体改变的存在和识别对于诊断和治疗决策很重要。识别染色体改变也可以导致更好的风险分类，这很重要，因为我们知道，虽然重排往往具有较差的结果，但一些重排实际上提供了更好的预后。随着白血病个体化、靶向治疗的未来，将常规细胞遗传学与分子和FISH方法相结合，将大大提高信息的准确性，为患者提供更具体、更定制的治疗选择。

While ALL is the most common childhood leukemia, it is not as commonly seen in adults. B cell ALL is more common than T cell ALL in all ages, and accounts for about 90% of ALL cases in children and about 75% of ALL cases in adults. Cure rates in children exceed 90% but in adults varies with age and depending on chromosomal alterations. Most B cell ALL subtypes with chromosome translocations tend to have a poorer outcome than those without translocations. As well, younger adults, <50 years old, have better prognosis than older adults.
虽然急性淋巴细胞白血病是最常见的儿童白血病，但在成人中并不常见。在所有年龄段，B细胞急性淋巴细胞白血病比T细胞急性淋巴细胞白血病更常见，约占儿童急性淋巴细胞白血病病例的90%，约占成人急性淋巴细胞白血病病例的75%。儿童的治愈率超过 90%，但成人的治愈率因年龄和染色体改变而异。大多数具有染色体易位的 B 细胞 ALL 亚型往往比没有易位的亚型预后更差。同样，<50 岁的年轻人比老年人预后更好。

This patient did not have a BCR/ABL rearrangement or MLL gene locus 11q23 translocation, which both carry poorer prognoses, but she also did not have a translocation between chromosome 12 and 21 or more than 50 chromosomes, both of which offer more favorable prognoses. This young woman therefore would be in an average risk category and appears to have been diagnosed very early in the course of her disease. We have not seen any further workup, as the patient is being treated at another facility. We wish her well in her leukemia treatments.
该患者没有 BCR/ABL 重排或 MLL 基因位点 11q23 易位，两者都预后较差，但她也没有在 12 号和 21 号染色体或超过 50 条染色体之间易位，两者都提供更有利的预后。因此，这名年轻女子属于平均风险类别，并且似乎在她的病程中很早就被诊断出来。我们没有看到任何进一步的检查，因为病人正在另一家机构接受治疗。我们祝愿她在白血病治疗中一切顺利。

References 引用

1. Hasle H, Heim S, Schroeder H, et al. Transient pancytopenia preceding acute lymphoblastic leukemia (pre-ALL). Leukemia. 1995 Apr;9(4):605-608.
   Hasle H、Heim S、Schroeder H 等人。急性淋巴细胞白血病前的一过性全血细胞减少症（ALL 前期）。白血病。1995年4月;9(4):605-608.

2. Iacobucci I, Mullighan CG. Genetic Basis of Acute Lymphoblastic Leukemia. J Clin Oncol. 2017 Mar 20;35(9):975-983. doi: 10.1200/JCO.2016.70.7836. Epub 2017 Feb 13. PMID: 28297628; PMCID: PMC5455679
   Iacobucci I，Mullighan CG。急性淋巴细胞白血病的遗传基础。J 临床肿瘤。2017年3月20日;35(9):975-983.doi：10.1200/JCO.2016.70.7836.Epub 格式 2017 2 月 13.PMID：28297628;PMCID：PMC5455679

3. Bone Marrow evaluation in new onset pancytopenia. Human Pathology. Vol 44, Issue 6. June 2013
   新发全血细胞减少症的骨髓评估。人类病理学。第 44 卷，第 6 期。2013 年 6 月

4. Hematology: Basic Principles and Practice, 7th Edition . Ronald Hoffman, Edward J. Benz, et al. 2018 Elsevier
   血液学：基本原理与实践，第 7 版。Ronald Hoffman， Edward J. Benz， et al. 2018 爱思唯尔

-Becky Socha, MS, MLS(ASCP) CM BB CM graduated from Merrimack College in N. Andover, Massachusetts with a BS in Medical Technology and completed her MS in Clinical Laboratory Sciences at the University of Massachusetts, Lowell. She has worked as a Medical Technologist for over 40 years and has taught as an adjunct faculty member at Merrimack College, UMass Lowell and Stevenson University for over 20 years.  She has worked in all areas of the clinical laboratory, but has a special interest in Hematology and Blood Banking. She currently works at Mercy Medical Center in Baltimore, Md. When she’s not busy being a mad scientist, she can be found outside riding her bicycle.
-Becky Socha，MS，MLS（ASCP） CM BB CM 毕业于马萨诸塞州安多弗的梅里马克学院，获得医学技术学士学位，并在马萨诸塞大学洛厄尔分校完成了临床实验室科学硕士学位。她担任医疗技术专家已有 40 多年，并在梅里马克学院、马萨诸塞大学洛厄尔分校和史蒂文森大学担任兼职教员 20 多年。她曾在临床实验室的所有领域工作过，但对血液学和血库特别感兴趣。她目前在马里兰州巴尔的摩的 Mercy 医疗中心工作。当她不忙于成为一名疯狂的科学家时，她可以在外面骑自行车。