A 73 year old African American female had a CBC ordered as part of routine pre-op testing before knee surgery. The order for a CBC/auto differential and was run on our Sysmex XN-3000. CBC results were unremarkable, with the exception of a decreased platelet count. However, the instrument flagged “Suspect, Left shift?” and a slide was made for review. The CBC results are shown in Table 1 below.
一名 73 岁的非裔美国女性在膝关节手术前常规术前检查中进行了 CBC。CBC/自动差速器的订单在我们的希森美康 XN-3000 上运行。全血细胞计数结果无明显异常，但血小板计数减少除外。然而，仪器标记了“嫌疑人，左移？”，并制作了一张幻灯片进行审查。全血细胞计数结果如下表1所示。
Table 1. CBC results on 73 year old female.
表 1.73岁女性的CBC结果。
Pelger-Huët anomaly (PHA), is a term familiar to medical laboratory professionals, but mostly from textbook images. PHA is considered to be rare, affecting about 1 in 6000 people. PHA has been found in persons of all ethnic groups and equally in men and women. The characteristic, morphologically abnormal neutrophils were first described by Dutch hematologist Pelger in 1928. He described neutrophils with dumbbell shaped, bi-lobed nuclei. The term ‘pince-nez’ has also been used to describe this spectacle shaped appearance. Pelger also noted that, in addition to hyposegmentation, there is an overly coarse clumping of nuclear chromatin. In 1931, Huët, a Dutch pediatrician, identified this anomaly as an inherited condition.
Pelger-Huët 异常 （PHA） 是医学实验室专业人员熟悉的术语，但主要来自教科书图像。PHA 被认为是罕见的，每 6000 人中约有 1 人受到影响。PHA存在于所有种族群体中，在男性和女性中也同样存在。1928 年，荷兰血液学家 Pelger 首次描述了这种特征性、形态异常的中性粒细胞。他描述了具有哑铃形双叶核的中性粒细胞。术语“pince-nez”也被用来描述这种奇观形状的外观。Pelger还指出，除了低分割外，核染色质还存在过于粗糙的聚集。1931 年，荷兰儿科医生 Huët 将这种异常确定为遗传性疾病。
Pelger-Huët anomaly is an autosomal dominant disorder caused by a mutation in the lamina B receptor (LBR) gene on band 1q42. This defect is responsible for the abnormal routing of the heterochromatin and nuclear lamins, proteins that control the shape of the nuclear membrane.
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Because of this mutation, nuclear differentiation is impaired, resulting in white blood cells with fewer lobes or segments. In classic inherited PHA, cells are the size of mature neutrophils and have very clumped nuclear chromatin. About 60-90% of these neutrophils are bi-lobed either with a thin filament between the lobes, or without the filament. About 10-40% of total neutrophils in PHA have a single, non-lobulated nucleus. Occasional normal neutrophils with three-lobed nuclei may be seen.
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Despite their appearance, Pelger-Huët cells are considered mature cells, function normally and therefore can fight infection. It is considered a benign condition; affected individuals are healthy and no treatment is necessary for PHA.
Pelger-Huët 异常是一种常染色体显性遗传病，由 1q42 条带上的层 B 受体 （LBR） 基因突变引起。这种缺陷是导致异染色质和核层粘连蛋白异常路由的原因，异染色质和核层粘连蛋白是控制核膜形状的蛋白质。
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由于这种突变，细胞核分化受损，导致白细胞的叶或节段减少。在经典的遗传性PHA中，细胞的大小与成熟的中性粒细胞相当，并且具有非常聚集的核染色质。这些中性粒细胞中约有60-90%是双叶的，裂片之间有细丝，或者没有细丝。PHA 中大约 10-40% 的中性粒细胞总粒细胞具有单个非分叶细胞核。偶尔可见具有三叶核的正常中性粒细胞。
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尽管它们看起来很漂亮，但 Pelger-Huët 细胞被认为是成熟细胞，功能正常，因此可以抵抗感染。它被认为是一种良性疾病;受影响的个体是健康的，PHA不需要治疗。
Automated instruments may flag a left shift when they detect these Pelger-Huët cells. In this patient, the analyzer flagged a left shift and a slide was made and sent to CellaVision. The CellaVision pre-classified the Pelger-Huët cells as neutrophils, bands, and myelocytes. All of the neutrophil images were either bi-lobed or non-lobed forms. None of the neutrophils had more than 2 lobes. Eosinophils also had poorly differentiated nuclei. Cell images from this patient can be seen in Images 1-4.
当自动仪器检测到这些 Pelger-Huët 细胞时，它们可能会标记左移。在这名患者中，分析仪标记了左移，并制作了一张幻灯片并发送到 CellaVision。CellaVision 将 Pelger-Huët 细胞预先分类为中性粒细胞、条带细胞和骨髓细胞。所有中性粒细胞图像均为双叶或非裂片形式。没有一个中性粒细胞有超过 2 个叶。嗜酸性粒细胞也具有分化不良的细胞核。该患者的细胞图像如图 1-4 所示。
Image 1. Images from CellaVision of bi-lobed “pince-nez” neutrophils with thin filament
图 1.来自 CellaVision 的图像，具有细丝的双叶“pince-nez”中性粒细胞
Image 2. Non-terminally differentiated neutrophils pre-classified as bands on CellaVision. Bilobed variant without the thin filament.
图 2.非终末分化的中性粒细胞在 CellaVision 上预先分类为条带。没有细丝的双叶变体。
Image 3. Non-lobed neutrophils with extremely coarse clumping of nuclear chromatin.
图 3.非裂片中性粒细胞，核染色质极粗。
Image 4. Eosinophils in Pelger-Huët Anomaly.
图 4.Pelger-Huët 异常中的嗜酸性粒细胞。
If PHA is considered benign, with no clinical implications, why is it important to note these cells on a differential report? This slide was referred to our pathologist for a review. The patient had several previous CBC orders, but no differentials in our LIS. The pathologist reviewed the slide and, based on 100% of these neutrophils being affected, he reported “Pelger-Huët cells present. The presence of non-familial Pelger-Huët anomaly has been associated with medication effect, chronic infections and clonal myeloid neoplasms.” Thus, the importance of reporting this anomaly if seen on a slide. If the instrument flags a left shift, this is typically associated with infection. If these cells are misclassified as bands and immature granulocytes, with no mention of the morphology, there would be a false increase in bands reported and the patient may be unnecessarily worked up for sepsis.
如果PHA被认为是良性的，没有临床意义，为什么在鉴别报告中注明这些细胞很重要？这张幻灯片被转介给我们的病理学家进行审查。患者之前有过几次全血细胞计数检查，但在我们的 LIS 中没有鉴别诊断。病理学家查看了载玻片，并根据 100% 的中性粒细胞受到影响，他报告说“存在 Pelger-Huët 细胞。非家族性 Pelger-Huët 异常的存在与药物效应、慢性感染和克隆性髓系肿瘤有关。因此，如果在幻灯片上看到这种异常情况，报告这种异常情况的重要性。如果仪器标记左移，这通常与感染有关。如果这些细胞被错误地归类为条带和未成熟粒细胞，而没有提及形态，则报告的条带会出现错误的增加，并且患者可能会不必要地接受脓毒症治疗。
An additional reason for reporting the presence of Pelger-Huët cells is that pelgeroid cells are also seen in a separate anomaly, called acquired or pseudo-Pelger-Huët anomaly (PPHA). PPHA is not inherited and can develop with acute or chronic myelogenous leukemia and in myelodysplastic syndrome. A type of PPHA may also be associated with infections or medications. Certain chemotherapy drugs, immunosuppressive drugs used after organ transplants, and even ibuprofen have been recognized as triggers for PPHA. PPHA caused by medications is typically transient and resolves after discontinuation of the drug. To add to causes, most recently, there have been studies published that report PPHA in COVID-19 patients.
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报告 Pelger-Huët 细胞存在的另一个原因是，Pelgeroid 细胞也出现在一个单独的异常中，称为获得性或假 Pelger-Huët 异常 （PPHA）。PPHA不是遗传性的，可与急性或慢性粒细胞性白血病以及骨髓增生异常综合征一起发展。一种类型的PPHA也可能与感染或药物有关。某些化疗药物、器官移植后使用的免疫抑制药物，甚至布洛芬都被认为是 PPHA 的诱因。药物引起的 PPHA 通常是短暂的，停药后消退。雪上加霜的是，最近有研究发表在COVID-19患者中报告了PPHA。
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With several different causes of PHA/PPHA, a differential diagnosis is important. Is this a benign inherited condition, a drug reaction that will self-resolve after therapy is stopped, or something more serious? If Pelger-Huët cell are reported, it is important for the provider to correlate this finding with patient symptoms, treatments and history. There was no medication history and little other medical history in our case patient’s chart, and no mention of inherited PHA. The patient had also been tested for COVID-19 with her pre-op testing and was COVID negative. On initial identification of Pelger-Huët, a benign diagnosis that needs no treatment or work up would be the best outcome, so an attempt could be made to determine if the patient has inherited PHA. If other family members are known to have this anomaly, this would be the likely diagnosis as PHA is autosomal dominant. Family members can also easily be screened with CBC and manual differential. Molecular techniques are available to confirm PHA but are not routinely used. In the absence of this anomaly in other family members, it would need to be determined if the patient was on any medications that can cause pelgeroid cells. Inherited PHA and drug induced PPHA should be ruled out first because PPHA can also be predicative of possible development of CML or MDS. Considering this cause first could lead to unnecessary testing that might include a bone marrow aspirate and biopsy. Additionally, the entire clinical picture should be reviewed because in PPHA associated with myeloproliferative disorders there is usually accompanying anemia and thrombocytopenia and the % of pelgeroid cells tends to be lower.
对于PHA/PPHA的几种不同病因，鉴别诊断很重要。这是一种良性遗传性疾病，还是在停止治疗后会自行消退的药物反应，还是更严重的事情？如果报告了 Pelger-Huët 细胞，提供者必须将这一发现与患者症状、治疗和病史相关联。在我们的病例患者图表中没有用药史，也几乎没有其他病史，也没有提到遗传性 PHA。该患者还通过术前检测接受了 COVID-19 检测，结果为 COVID 阴性。在初步确定 Pelger-Huët 时，不需要治疗或检查的良性诊断将是最佳结果，因此可以尝试确定患者是否遗传了 PHA。如果已知其他家庭成员有这种异常，这将是可能的诊断，因为 PHA 是常染色体显性遗传的。家庭成员也可以很容易地通过全血细胞计数和手动分类检查进行筛查。分子技术可用于确认 PHA，但不常规使用。在其他家庭成员中没有这种异常的情况下，需要确定患者是否正在服用任何可能导致鳕皮细胞的药物。应首先排除遗传性 PHA 和药物诱导的 PPHA，因为 PPHA 也可能预示着 CML 或 MDS 的可能发展。首先考虑这个原因可能会导致不必要的检查，可能包括骨髓穿刺和活检。此外，应回顾整个临床表现，因为在与骨髓增生性疾病相关的 PPHA 中，通常伴有贫血和血小板减少症，并且 pelgeroid 细胞的百分比往往较低。
Today most clinical laboratories have instruments that do automated differentials, and we encourage physicians to order these because they are very accurate and count thousands of cells compared to the 100 cells counted by a tech on a manual differential. Automated differentials are desirable for consistency and to improve turnaround times. Yet, it is important to know when a slide needs to be reviewed under the scope or with CellaVision. If a patient presents with a normal WBC and a left shift on the auto diff with no apparent reason, pictures can reveal important clinical information. Awareness of different causes of PHA/PPHA can relieve anxiety in patients and prevent extensive, unnecessary testing and invasive procedures.
如今，大多数临床实验室都有进行自动分类的仪器，我们鼓励医生订购这些仪器，因为它们非常准确，可以计数数千个细胞，而技术人员在手动分类中只能计数 100 个细胞。自动差速器对于一致性和缩短周转时间是可取的。然而，重要的是要知道何时需要在示波器下或使用 CellaVision 审查幻灯片。如果患者表现为白细胞正常且无明显原因的自动快标左移，则图片可以揭示重要的临床信息。了解 PHA/PPHA 的不同病因可以缓解患者的焦虑，并防止广泛、不必要的检查和侵入性手术。
Ayan MS, Abdelrahman AA, Khanal N, Elsallabi OS, Birch NC. Case of acquired or pseudo-Pelger-Huët anomaly.
Oxf Med Case Reports
. 2015;2015(4):248-250. Published 2015 Apr 1. doi:10.1093/omcr/omv025
Ayan MS、Abdelrahman AA、Khanal N、Elsallabi OS、Birch NC。获得性或假性 Pelger-Huët 异常的情况。Oxf Med 病例报告。2015;2015(4):248-250.发布时间：2015 年 4 月 1 日。doi：10.1093/omcr/omv025
Alia Nazarullah, MD; Christine Liang, MD; Andrew Villarreal, MLS; Russell A. Higgins, MD; Daniel D. Mais, MD. Am J Clin Peripheral Blood Examination Findings in SARS-CoV-2 Infection . Pathol. 2020;154(3):319-329.
Alia Nazarullah，医学博士;Christine Liang，医学博士;安德鲁·比利亚雷亚尔，MLS;Russell A. Higgins，医学博士;丹尼尔 D. Mais，医学博士。SARS-CoV-2 感染的 Am J Clin 外周血检查结果。病理学。2020;154(3):319-329.
-Becky Socha, MS, MLS(ASCP)
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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 30 years. She’s worked in all areas of the clinical laboratory, but has a special interest in Hematology and Blood Banking. When she’s not busy being a mad scientist, she can be found outside riding her bicycle.
-Becky Socha，MS，MLS（ASCP）
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