leukocytosis

白细胞增多
  • 文章类型: Journal Article
    背景:中性粒细胞增多是中性粒细胞数量增加超过7.5×103/μL。白细胞增加超过50×103/μL称为类白血病反应;当它与实体瘤相关时,它被认为是一种副肿瘤综合征,称为副肿瘤类白血病反应(PLR).这是一种非常罕见的临床疾病,与癌肉瘤有关的情况非常罕见。我们介绍了2023年5月至9月在萨拉曼卡大学医院肿瘤科观察到的两例类白血病反应。我们文章的主要目的是描述在诊断癌肉瘤癌肉瘤时副肿瘤白细胞增多的异常出现,详细解释其诊断程序,并显示与之相关的不良预后。
    方法:在我们的演讲中,我们描述了两种类似的情况:首先,一名60岁女性,无相关病史。2023年8月,她的主治医师因虚弱而转诊至内科,腰椎疼痛,和体重减轻12公斤3个月的进化。体格检查发现明显的胃下肿块。一个腹部,骨盆,和胸部计算机断层扫描(CT)扫描显示不均匀的固体肿块,坏死区域起源于子宫。解剖病理学诊断为癌肉瘤。该患者的肾功能进行性恶化,与170×103/μL中性粒细胞引起的高白细胞增多继发的高粘滞相关。在第二种情况下,我们描述了继发于肾癌肉瘤的PLR的诊断。当病人开始化疗时,他呈现55.08×103/μL白细胞,53.16×103/μL中性粒细胞。接受化疗后八天,患者因少尿症和意识下降而入院。他的肌酐为6.25mg/dL,磷酸盐12.4mg/dL,白细胞1.05×103/μL,中性粒细胞0.71×103/μL。临床诊断为与肿瘤溶解综合征和3级中性粒细胞减少相关的多因素混合(肾脏和肾前)慢性肾脏疾病急性加重。病人表现出较差的进化,2个月后死亡。
    结论:PLR是一种与不同类型实体瘤相关的严重副肿瘤综合征。它在诊断肿瘤时的出现意味着不良的预后。
    BACKGROUND: Neutrophilia is an increase in the number of neutrophils over 7.5×103/µL. An increase in leukocytes over 50×103/µL is called a leukemoid reaction; and when it is associated with a solid tumor, it is considered a paraneoplastic syndrome called paraneoplastic leukemoid reaction (PLR). It is a very rare clinical condition and it is very unusual for it to be associated with carcinosarcoma. We present two cases of a leukemoid reaction observed in the Medical Oncology Department of the University Hospital of Salamanca between May and September 2023. The main objectives of our article are to describe the unusual appearance of paraneoplastic leukocytosis at the diagnosis of carcinosarcoma carcinosarcoma, explain in a detailed way its diagnostic procedure and to show the poor prognosis to which it is associated.
    METHODS: In our presentation, we describe two similar cases: first of all, a 60-year-old woman without relevant medical history. She was referred by her primary physician to the Department of Internal Medicine in August 2023 with asthenia, lumbar pain, and weight loss of 12 kg of 3 months of evolution. The physical examination revealed a palpable hypogastric mass. An abdominal, pelvic, and thoracic computed tomography (CT) scan revealed a heterogenous solid mass with necrotic areas originating in the uterus. The anatomopathological diagnosis was carcinosarcoma. The patient showed a progressive worsening in her renal function associated with hyperviscosity secondary to hyperleukocytosis caused by 170×103/µL neutrophils. In the second case we describe the diagnosis of a PLR secondary to a kidney carcinosarcoma. When the patient started chemotherapy, he presented 55.08×103/µL leukocytes, 53.16×103/µL neutrophils. Eight days after receiving chemotherapy, the patient was admitted as an emergency with oligoanuria and decreased consciousness. He presented creatinine 6.25 mg/dL, phosphate 12.4 mg/dL, leukocytes 1.05×103/µL, and neutrophils 0.71×103/µL. The clinical diagnosis was acute exacerbation of multifactorial mixed (renal and prerenal) chronic kidney disease associated with tumor lysis syndrome and grade 3 neutropenia. The patient presented a poor evolution, dying after 2 months.
    CONCLUSIONS: PLR is a severe paraneoplastic syndrome associated with different types of solid tumors. Its appearance at the time of diagnosis of a tumor implies a poor vital prognosis.
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  • 文章类型: Case Reports
    很少有B细胞急性淋巴细胞白血病(B-ALL)-嗜酸性粒细胞增多(ALL-eo)关联的报道。外周血涂片(PBS)中缺乏或不存在原始细胞以及荨麻疹,发烧,关节痛,肌痛,出汗,呼吸困难是这种情况的常见特征。在这里,我们报告了一名16岁的男性患者,因荨麻疹和全身性瘙痒入院。PBS进行了检查,和嗜酸性粒细胞(90%)在不同的领域。然而,在PBS中没有看到原始细胞。在骨髓检查中,据报道,末端脱氧核苷酸转移酶阳性和CD20阳性淋巴母细胞以及嗜酸性粒细胞增多.最终,患者的B-ALL诊断得到证实,他开始接受柏林-法兰克福-明斯特化疗方案。B-ALL与嗜酸性粒细胞增多的关联是一种罕见的疾病。我们希望此病例报告和文献综述可以帮助临床医生正确处理这种罕见的情况。
    Few cases of B-cell acute lymphoblastic leukemia (B-ALL)-eosinophilia (ALL-eo) association have been reported. The lack or absence of blasts in the peripheral blood smear (PBS) along with urticarial rash, fever, arthralgia, myalgia, sweating, and dyspnea are common features of this condition. Herein, we report a 16-year-old male patient admitted to the emergency department with urticaria and generalized itching. PBS was examined, and eosinophils (90%) were seen in different fields. However, blast cells were not seen in PBS. In a bone marrow examination, terminal deoxynucleotidyl transferase-positive and CD20-positive lymphoid blasts were reported along with eosinophilia. Eventually, the B-ALL diagnosis was confirmed for the patient, and he was started on the Berlin-Frankfurt-Münster chemotherapy regimen. The association of B-ALL with hypereosinophilia is a rare condition. We hope this case report and literature review can help clinicians to manage this rare condition properly.
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  • 文章类型: Case Reports
    婴儿白血病是一种罕见的血液癌症,在生命的第一年内表现出来。这种恶性肿瘤具有高度侵袭性,并具有独特的免疫表型,细胞遗传学,和分子属性。它可以起源于髓样或淋巴样细胞。它通常在女性中表现出更高的发病率。
    1个月大的男婴,最初看起来很健康,表现出烦躁和喂养困难。出生时没有并发症,常规新生儿评估似乎正常,体格检查没有异常。然而,实验室检测显示白细胞计数极高,低血小板,血红蛋白升高.进一步的检查显示白细胞计数为1450×106/l,血膜显示出以原始细胞为主的显着白细胞增多。腹部超声证实肝脾肿大在怀孕期间不存在。随后的骨髓分析和流式细胞术确定了B细胞急性淋巴细胞白血病(B-ALL)的诊断。
    婴儿ALL在出生后的第一个月内很少出现。在大多数情况下,诊断是在出生前确定的。当特征性体征如肝脾肿大时,皮肤白血病,或者存在髓外和中枢神经系统的浸润性受累,产后诊断相对简单.然而,在某些情况下,儿童出现类似于其他疾病的非特异性和模棱两可的症状。
    这个案例强调了儿科医生保持警惕和调整细微指标的重要性,这些指标可以将常见疾病与婴儿ALL等严重疾病区分开来。
    UNASSIGNED: Infantile leukaemia is an uncommon haematological cancer that manifests within the first year of life. This malignancy is highly aggressive and possesses distinctive immunophenotypic, cytogenetic, and molecular attributes. It can originate from either myeloid or lymphoid cells. It often exhibits a higher incidence among females.
    UNASSIGNED: A 1-month-old male infant, initially seemingly healthy, presented with irritability and feeding difficulties. Born without complications, routine neonatal assessments appeared normal, and physical examination revealed no abnormalities. However, laboratory tests indicated an extremely high white blood cell count, low platelets, and elevated haemoglobin. Further examinations showed a white blood cell count of 1450 × 106/l with a blood film revealing significant leukocytosis dominated by blast cells. Abdominal ultrasound confirmed hepatosplenomegaly which was not present during pregnancy. Subsequent bone marrow analysis and flow cytometry established a diagnosis of B-cell acute lymphoblastic leukaemia (B-ALL).
    UNASSIGNED: It is rare for infantile ALL to manifest within the first month after birth. In most cases, the diagnosis is established before birth. When characteristic signs such as hepatosplenomegaly, leukaemia cutis, or infiltrative involvement of the extramedullary and central nervous systems are present, postnatal diagnoses are relatively straightforward. However, there are instances where children present with non-specific and ambiguous symptoms that resemble other medical conditions.
    UNASSIGNED: This case underscores the importance of paediatricians being vigilant and attuned to the subtle indicators that differentiate common illnesses from serious conditions such as infantile ALL.
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  • 文章类型: Meta-Analysis
    尽管做出了种种努力,结核病(TB)仍然是全球十大主要死亡原因之一。造血系统受到TB的严重影响,关于TB患者的血液学特征的信息很少。在这方面,本系统综述和荟萃分析旨在评估新诊断的TB患者的血液学参数.直到2023年4月,通过在PubMed数据库中搜索找到相关论文。包括15篇论文,涉及3354名患者。单样本荟萃分析显示,在新诊断的结核病患者中,Hgb的合并平均值较低,为11.679g/dl(95%CI:10.982-12.377),合并ESR增加为63.569mm/h(95%CI:57.834-69.304)。贫血的汇总患病率,白细胞增多,血小板增多症,淋巴细胞减少率为61.6%(95%CI:45.4-75.6%),45.9%(95%CI:39.1-52.9%),结核病患者之间的31.9%(95CI:15-55.3%)和23.1%(95CI:5.4-61.5%),分别。从两个样本的荟萃分析中,结核病患者的RBC和HgB值显着低于健康对照组(p<0.05)。意识到常见的血液异常,如血沉升高,白细胞增多,新诊断的结核病患者的贫血有助于医生早期诊断和更好地管理疾病。
    Despite all efforts, tuberculosis (TB) remains one of the 10 leading causes of death worldwide. The hematopoietic system is seriously affected by TB and there is little information about the hematological profile of patients with TB. In this regard, this systematic review and meta-analysis aimed to assess hematological parameters among newly diagnosed TB patients. Relevant papers were found by searching in the PubMed database until April 2023. Fifteen papers involving 3354 patients were included. One-sample meta-analysis revealed the low pooled mean values for Hgb of 11.679 g/dl (95 % CI: 10.982-12.377) and the increased pooled ESR of 63.569 mm/h (95 % CI: 57.834-69.304) among newly diagnosed TB patients. The pooled prevalence of anemia, leukocytosis, thrombocytosis, and lymphopenia was 61.6 % (95 % CI: 45.4-75.6 %), 45.9 % (95 % CI: 39.1-52.9 %), 31.9 % (95%CI: 15-55.3 %) and 23.1 % (95%CI: 5.4-61.5 %) between TB patients, respectively. From a two-sample meta-analysis, the RBC and HgB values for TB patients were significantly lower than that of healthy controls (p < 0.05). Awareness of common blood abnormalities like elevated ESR, leukocytosis, and anemia in newly diagnosed TB patients helps physicians in early diagnosis and better management of disease.
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  • 文章类型: Systematic Review
    脑淋巴瘤(LC)是一种罕见的原发性中枢神经系统淋巴瘤,非强化浸润性病变,常被误诊。我们的研究旨在通过分析来自文献和我们自己的中心的患者来探讨LC的临床特征和预后。从而提高早期诊断和治疗。PubMed,审查了WebofScience和我们医院的数据库,和人口统计信息,临床,病态,脑脊液(CSF),提取神经影像学和治疗方案.通过生成存活曲线并使用对数秩检验进行比较来进行单变量存活曲线分析。使用Cox比例风险回归模型进行多变量分析以确定预后预测因子。共有81名患者(中位年龄:58岁;四分位距,IQR:50-66.5年),45名男性和36名女性,包括在内。最常见的症状是认知障碍(65.4%)和步态障碍(50.6%)。影像学检查显示81例患者均有幕上结构受累,93.8%(76/81)有双侧半球受累。53.3%(32/60)的患者出现CSF细胞增多,65%(39/60)的患者出现CSF蛋白水平升高。中位诊断时间为4.8个月(IQR:2.3-6.9个月)。与所有81例患者的4个月(95%CI:1.78-6.22)相比,接受化疗加放疗的患者的中位OS为20个月(95%CI:8.24-31.76).多因素Cox分析显示,放化疗(HR:0.12;95%CI:0.02-0.68)和较高的CSF葡萄糖水平(HR:0.01;95%CI:0.00-0.26)与死亡呈负相关。当神经影像学检查伴有双侧半球受累和CSF异常并伴有细胞增多和蛋白质增加时,应提醒LC的诊断。一旦确诊,如果患者的身体条件允许,可以考虑化疗和放疗的结合。期刊标准指令需要非结构化摘要。请检查并确认。我们已经检查并确认没有问题。
    Lymphomatosis cerebri (LC) is a rare type of primary central nervous system lymphoma with diffuse, nonenhancing infiltrative lesions and is often misdiagnosed. Our study aimed to investigate the clinical characteristics and prognosis of LC through analyzing patients from the literature and our own center, so as to improve early diagnosis and treatment. PubMed, Web of Science and our hospital databases were reviewed, and information on demographic, clinical, pathological, cerebrospinal fluid (CSF), neuroimaging and treatment options was extracted. Univariate survival analysis was conducted by generating survival curves and comparing them using the log-rank test. Multivariate analysis was performed using the Cox proportional hazards regression model to identify the prognostic predictors. A total of 81 patients (median age: 58 years; interquartile range, IQR: 50-66.5 years), 45 males and 36 females, were included. The most common symptoms were cognitive impairment (65.4%) and gait impairment (50.6%). Imaging studies indicated that all 81 patients had supratentorial structure involvement, and 93.8% (76/81) had bilateral hemisphere involvement. There were 53.3% (32/60) patients with CSF pleocytosis and 65% (39/60) patients with increased CSF protein levels. The median time of diagnosis was 4.8 months (IQR: 2.3-6.9 months). Compared with 4 (95% CI: 1.78-6.22) months for all 81 patients, the median OS was 20 (95% CI: 8.24-31.76) months for those who had chemotherapy plus radiotherapy. Multivariate Cox analysis revealed that chemoradiotherapy (HR: 0.12; 95% CI: 0.02-0.68) and higher CSF glucose level (HR: 0.01; 95% CI: 0.00-0.26) were inversely associated with death. The diagnosis of LC should be alerted when neuroimaging with bilateral hemispheric involvement and CSF abnormality with pleocytosis and increased protein. Once the diagnosis is confirmed, the combination of chemotherapy and radiotherapy can be considered if the patient\'s physical condition permits.Journal standard instruction requires an unstructured abstract. Kindly check and confirm.We have checked and confirmed that there is no problem.
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  • 文章类型: Review
    慢性淋巴细胞白血病(CLL)是一种克隆成熟的B细胞肿瘤,具有典型的惰性临床病程。尽管大多数临床医生仅通过观察这些肿瘤,向淋巴细胞白血病的积极转变,弥漫性大B细胞淋巴瘤(Richter转化)或经典霍奇金淋巴瘤需要立即关注。我们在先前诊断的CLL患者中介绍了一例极端白细胞增多症(>1百万/μL)。由于有症状的白细胞淤滞,她开始接受细胞减灭术治疗,包括白细胞分离术。经过三轮白细胞分离术(LCP)和同步化疗,她的白细胞计数从最大1262×103/μL下降到574×103/μL。据我们所知,具有需要治疗性LCP的症状性白细胞淤滞的CLL在文献中很少报道。我们认为治疗性LCP在如此罕见的情况下是有价值的,但像我们的案子一样危险的环境。
    Chronic lymphocytic leukemia (CLL) is a clonal mature B-cell neoplasm with a typically indolent clinical course. Though most clinicians follow these neoplasms through observation alone, an aggressive transformation to prolymphocytic leukemia, diffuse large-B-cell lymphoma (Richter transformation) or classical Hodgkin lymphoma requires immediate attention. We present a case of extreme leukocytosis (>1 million/μL) in a previously diagnosed CLL patient. Due to symptomatic leukostasis, she was started on cytoreductive therapies including leukocytapheresis. After three rounds of leukocytapheresis (LCP) and concurrent chemotherapy, her white blood cell count decreased from a maximum 1262 × 103 /μL to 574 × 103 /μL. To our knowledge, CLL with symptomatic leukostasis that required therapeutic LCP is rarely reported in literature. We propose that therapeutic LCP is of value in such rare, yet dangerous settings like our case.
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  • 文章类型: Review
    暂无摘要。
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  • 文章类型: Review
    粒细胞集落刺激因子(G-CSF)糖蛋白刺激骨髓中的前体细胞增殖和分化。已经报道了各种产生G-CSF的肿瘤;它们显示出早期进展和极差的预后。这里,我们报告一例产生G-CSF的胆囊癌伴淋巴结转移。此外,我们回顾了以前30例产生G-CSF的胆囊癌的病例报告,以阐明其特征和最合适的治疗方法.在例行拜访当地医生以监测糖尿病和高血压的过程中,一名68岁的女性被发现白细胞(WBC)计数和C反应蛋白(CRP)水平升高,和胆囊肿块.实验室检查显示血清G-CSF水平很高,影像学显示胆囊肿瘤伴局部淋巴结肿大。我们诊断为产生G-CSF的胆囊癌,并进行了IVa/V段的肝切除术:区域淋巴结清扫术和肝外胆管切除术。病理上,肿瘤为低分化鳞状细胞癌。肿瘤细胞G-CSF免疫染色阳性。手术后16个月,她还活着,没有复发。如果患者出现胆囊肿瘤,白细胞计数和CRP水平升高,但没有感染症状,应怀疑产生G-CSF的胆囊癌;诊断后应立即进行根治性切除。
    The granulocyte-colony-stimulating factor (G-CSF) glycoprotein stimulates precursor cell proliferation and differentiation in the bone marrow. Various G-CSF-producing tumors have been reported; they showed early progression and an extremely poor prognosis. Here, we report a case of G-CSF-producing gallbladder cancer with lymph node metastasis. In addition, we reviewed 30 previous case reports of G-CSF-producing gallbladder cancers to elucidate the characteristics and most appropriate treatment. During a routine visit to her local doctor for monitoring of diabetes and hypertension, a 68-year-old female was found to have an elevated white-blood-cell (WBC) count and C-reactive protein (CRP) level, and a gallbladder mass. Laboratory tests revealed a high serum G-CSF level, and imaging revealed a tumor of the gallbladder with regional lymphadenopathy. We diagnosed a G-CSF-producing gallbladder cancer and performed liver resection of segment IVa/V: regional lymph node dissection with extrahepatic bile duct resection. Pathologically, the tumor was a poorly differentiated squamous cell carcinoma. G-CSF immunostaining for tumor cells was positive. She is alive without recurrence at 16 months after surgery. If a patient exhibits a gallbladder tumor, with an elevated WBC count and CRP level but no symptoms of infection, a G-CSF-producing gallbladder cancer should be suspected; radical resection should be performed immediately after diagnosis.
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  • 文章类型: Review
    背景:一些病例报告描述了髓鞘少突胶质细胞糖蛋白抗体(MOG-Ab)相关脱髓鞘综合征患者出现无菌性脑膜炎症状。所有这些患者都需要免疫治疗。我们报告了一名患有MOG-Ab相关疾病(MOGAD)的患者,该患者出现无菌性脑膜炎症状,未经治疗即可改善。
    方法:一名13岁女孩出现发烧,头痛,食欲下降,颈部僵硬。脑脊液(CSF)分析显示细胞增多,磁共振成像(MRI)显示软脑膜增强。患者入院时被诊断为无菌性脑膜炎。然而,入院后4天没有恢复的迹象(即,发病后8天)。因此,我们进行了广泛的调查,以确定潜在感染和炎症的原因.入院后第14天,入院时进行的血清MOG-Ab检测呈阳性(1:128),她被诊断为MOGAD.她在入院后第18天出院,因为她的症状,CSF细胞增多,MRI检查结果有所改善。出院后约6周,MRI显示高强度无钆增强。然而,血清MOG-Ab试验为阴性.我们进行了11个月的随访,但没有发现新的神经系统症状。
    结论:据我们所知,这是首例MOGAD儿科患者在长期随访期间出现自发缓解且无脱髓鞘症状的报告.
    BACKGROUND: A few case reports have described patients with myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-associated demyelinating syndrome who presented with symptoms of aseptic meningitis. All such patients required immunotherapy. We report a patient with MOG-Ab-associated disorder (MOGAD) who presented with symptoms of aseptic meningitis and improved without treatment.
    METHODS: A 13-year-old girl presented with fever, headache, decreased appetite, and neck stiffness. Cerebrospinal fluid (CSF) analysis revealed pleocytosis and magnetic resonance imaging (MRI) showed leptomeningeal enhancement. The patient was diagnosed with aseptic meningitis at admission. However, there were no signs of recovery 4 days after admission (i.e., 8 days after disease onset). Therefore, we performed extensive investigations to identify the cause of the underlying infection and inflammation. On day 14 after admission, the serum MOG-Ab test performed at admission came back positive (1:128) and she was diagnosed with MOGAD. She was discharged on day 18 after admission, because her symptoms, CSF pleocytosis, and MRI findings had improved. About 6 weeks after discharge, MRI revealed hyperintensity without gadolinium enhancement. However, her serum MOG-Ab test was negative. We did follow-ups for 11 months but found no new neurological symptoms.
    CONCLUSIONS: To the best of our knowledge, this is the first ever report of a pediatric patient with MOGAD experiencing spontaneous remission with no demyelinating symptoms during an extended follow-up period.
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  • 文章类型: Case Reports
    与肿瘤细胞分泌的激素和细胞因子相关的系统作用可引起副肿瘤综合征。类白血病反应和高钙血症是副肿瘤综合征的相对常见表现。这里,我们描述了一例90岁女性患者,该患者出现白细胞增多和高钙血症,被诊断为产生粒细胞集落刺激因子(G-CSF)的宫颈癌,甲状旁腺激素相关蛋白(PTHrP)水平升高.患者就诊于我院,抱怨全身疲劳和厌食症。一入场,她出现了明显的白细胞增多,高钙血症,和C反应蛋白水平的增加。在腹部磁共振成像和组织病理学检查的基础上,患者被诊断为宫颈癌。额外的测试证实G-CSF的血浆水平升高,PTHrP,和血清白细胞介素-6.宫颈病理标本免疫染色显示肿瘤细胞中G-CSF的表达。该患者被诊断患有产生G-CSF的宫颈癌,并伴有PTHrP水平升高。作为高钙血症的治疗方法,停用口服维生素D衍生物和给予生理盐水和elcatonin无效,并且需要使用唑来膦酸水合物进行治疗干预。考虑到病人的高龄,未进行宫颈癌手术切除.住院后约3个月,她死于充血性心力衰竭。该病例被认为是副肿瘤综合征,其中G-CSF和PTHrP诱导的白细胞增多和高钙血症。据我们所知,没有关于产生G-CSF的宫颈癌的PTHrP水平升高的报道,我们的案子是第一份报告.
    Systemic effects associated with hormones and cytokines secreted by tumor cells can cause paraneoplastic syndrome. Leukemoid reactions and hypercalcemia are relatively common manifestations of paraneoplastic syndrome. Here, we describe the case of a 90-year-old woman who presented with leukocytosis and hypercalcemia and was diagnosed with granulocyte-colony stimulating factor (G-CSF)-producing cervical cancer with elevated levels of parathyroid hormone-related protein (PTHrP). The patient visited our hospital complaining of general fatigue and anorexia. On admission, she presented with marked leukocytosis, hypercalcemia, and an increase in C-reactive protein level. On the basis of abdominal magnetic resonance imaging and histopathological examination, the patient was diagnosed with cervical cancer. Additional tests confirmed elevated plasma levels of G-CSF, PTHrP, and serum interleukin-6. Immunostaining of pathological specimens of the uterine cervix showed expression of G-CSF in tumor cells. The patient was diagnosed with G-CSF-producing cervical cancer accompanied by elevation of PTHrP levels. As a treatment for hypercalcemia, discontinuation of oral vitamin D derivative and administration of saline and elcatonin were ineffective, and therapeutic intervention with zoledronic acid hydrate was required. Considering the patient\'s advanced age, surgical resection of cervical cancer was not performed. She died from congestive heart failure approximately 3 months after hospitalization. This case was indicated to be a paraneoplastic syndrome in which G-CSF and PTHrP-induced leukocytosis and hypercalcemia. To the best of our knowledge, there have been no reports of G-CSF-producing cervical cancer with elevated PTHrP levels, and our case is the first report.
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