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Kuo YC, Huang CY, Ng CCY, Lin CY, Huang WK, Lee LY, Fan HC, Lin AC, Yu KJ, Pang ST, Teh BT, Hsu CL. Paraneoplastic leukocytosis induces NETosis and thrombosis in bladder cancer PDX model. Am J Cancer Res 2024; 14:3694-3710. [PMID: 39267669 PMCID: PMC11387854 DOI: 10.62347/ihio5742] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2024] [Accepted: 05/08/2024] [Indexed: 09/15/2024] Open
Abstract
Paraneoplastic leukocytosis (PNL) in genitourinary cancer, though rare, can indicate aggressive behavior and poor outcomes. It has been potentially linked to cancer expressing G-CSF and GM-CSF, along with their respective receptors, exerting an autocrine/paracrine effect. In our study, we successfully established four patient-derived xenograft (PDX) lines and related cell lines from urothelial cancer (UC), conducting next-generation sequencing (NGS) for genetic studies. UC-PDX-LN1, originating from bladder cancer, exhibited two druggable targets - HRAS and ERCC2 - responding well to chemotherapy and targeted therapy, though not to tipifarnib, an HRAS inhibitor. Transcriptome analysis post-treatment illuminated potential mechanisms, with index protein analysis confirming their anticancer pathways. Mice implanted with UC-PDX-LN1 mirrored PNL observed in the patient's original tumor. Cytokine array and RT-PCR analyses revealed high levels of G-CSF and GM-CSF in our PDX and cell lines, along with their presence in culture media and tumor cysts.Leukocytosis within small vessels in and around the tumor, associated with NETosis and thrombus formation, suggested a mechanism wherein secreted growth factors were retained, further fueling tumor growth via autocrine/paracrine signaling. Disrupting this cancer cell-NETosis-thrombosis cycle, we demonstrated that anti-neutrophil or anticoagulant interventions enhanced chemotherapy's antitumor effects or prolonged survival in mice, even though these drugs lacked direct antitumor efficacy when used independently. Clinical observations in bladder cancer patients revealed PNL in 1.61% of cases (35/2162) with associated poor prognosis. These findings propose a novel approach, advocating for the combination of anticancer/NETosis/thrombosis strategies for managing UC patients presenting with PNL in clinical settings.
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Affiliation(s)
- Yung-Chia Kuo
- Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Chang Gung University Taoyuan 33305, Taiwan
| | - Chen-Yang Huang
- Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Chang Gung University Taoyuan 33305, Taiwan
| | - Cedric Chuan Young Ng
- Integrated Genomics Platform, National Cancer Centre Singapore Singapore, The Republic of Singapore
| | - Chiao-Yun Lin
- Gynecologic Cancer Research Center, Chang Gung Memorial Hospital at Linkou, Chang Gung University Taoyuan 33305, Taiwan
| | - Wen-Kuan Huang
- Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Chang Gung University Taoyuan 33305, Taiwan
| | - Li-Yu Lee
- Department of Pathology, Chang Gung Memorial Hospital at Linkou, Chang Gung University Taoyuan 33305, Taiwan
| | - Hsien-Chi Fan
- Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Chang Gung University Taoyuan 33305, Taiwan
| | - An-Chi Lin
- Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Chang Gung University Taoyuan 33305, Taiwan
| | - Kai-Jie Yu
- Division of Urology, Department of Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University Taoyuan 33305, Taiwan
| | - See-Tong Pang
- Division of Urology, Department of Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University Taoyuan 33305, Taiwan
| | - Bin Tean Teh
- Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR) Singapore, The Republic of Singapore
- Duke-NUS Medical School Singapore, The Republic of Singapore
| | - Cheng-Lung Hsu
- Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Chang Gung University Taoyuan 33305, Taiwan
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Yarih GOD, Bryan HRW, Antonio OJJ, Paulina MFA, Claudia CS, Alamilla-García G, Kuauhyama LO. Paraneoplastic Leukemoid reaction in soft tissue sarcoma: A case report and literature review. Int J Surg Case Rep 2024; 120:109819. [PMID: 38875823 PMCID: PMC11225176 DOI: 10.1016/j.ijscr.2024.109819] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Revised: 05/21/2024] [Accepted: 05/25/2024] [Indexed: 06/16/2024] Open
Abstract
INTRODUCTION Paraneoplastic leukemoid reactions (PLRs) in the context of sarcomas represent a unique clinical entity that poses significant diagnostic challenges and adds valuable insights to the surgical literature. Characterized by an abnormal elevation of white blood cell count, these reactions are often associated with aggressive tumor biology and poor prognosis, emphasizing the need for heightened awareness among clinicians. CASE PRESENTATION A 48-year-old male presented with a rapidly growing, ulcerated tumor on his thigh. Lab tests revealed an extreme leukocytosis with a white blood cell count of 92,860/mm3. Imaging and biopsy confirmed a high-grade spindle cell sarcoma. CLINICAL DISCUSSION After excluding other causes of leukocytosis, a PLR secondary to sarcoma was diagnosed. Despite initial antibiotic treatment, leukocytosis persisted, prompting a decision for surgical intervention. The patient underwent successful tumor resection, resulting in a significant decrease in leukocyte count and subsequent stable recovery, supported by adjuvant radiotherapy. CONCLUSION This case underscores the importance of recognizing PLRs in sarcoma patients as they can significantly impact clinical management and prognosis. It highlights the necessity of a multidisciplinary approach for accurate diagnosis and effective treatment. The case contributes to the surgical literature by detailing the diagnostic process and therapeutic interventions in managing such complex presentations, thereby providing key "take-away" lessons on the importance of considering PLRs in the differential diagnosis of leukocytosis in patients with malignancies.
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Affiliation(s)
- Garcia-Ortega Dorian Yarih
- Surgical Oncology, Skin, Soft Tissue & Bone Tumors Department, National Cancer Institute, Mexico City, Mexico.
| | | | | | | | | | | | - Luna-Ortiz Kuauhyama
- Surgical Oncology Department of Head and Neck Surgery Department, National Cancer Institute, Mexico City, Mexico
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Khan MUA, Shehryar A, Imran M, Ch MB, Baig A. An Uncommon Presentation of Paraneoplastic Leukemoid Reaction (PLR) in a Rare Case of Adenosquamous Carcinoma (ASC) of the Gallbladder (GB): A Case Report. Cureus 2023; 15:e41040. [PMID: 37519607 PMCID: PMC10373944 DOI: 10.7759/cureus.41040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/27/2023] [Indexed: 08/01/2023] Open
Abstract
This case report describes an unusual paraneoplastic leukemoid response presenting in a rare instance of gallbladder (GB) adenosquamous carcinoma (ASC). Adenocarcinoma is the most prevalent histological subtype of GB carcinoma, which is most frequently diagnosed in people in their sixth and seventh decades of life. Adenosquamous and squamous variations are uncommon. Rarely have reports of paraneoplastic leukemoid reaction (PLR) in GB carcinoma been made; this reaction is characterized by a white cell count exceeding 50,000/mm3 in combination with solid malignancy. PLR has most commonly been found in association with lung carcinoma. In this instance, a 40-year-old man presented with right upper abdominal pain and a total leukocyte count of 26 x 109/L. The patient was initially treated on the lines of acute cholecystitis. But when the abdominal symptoms and leukocytosis did not settle, open cholecystectomy was performed. The results of the histopathological analysis showed that the GB had adenosquamous cancer. The white cell count increased even after surgery. Leukocytosis in the patient was looked into further to rule out hematological malignancy and other possible reasons. Sadly, the patient expired before any treatment could be started. The cancer GB carcinoma is uncommon and aggressive. Despite its rarity, ASC should be included in the differential diagnosis. PLR is an unusual manifestation associated with GB carcinoma. A thorough investigation, including a complete blood count, can help identify this paraneoplastic syndrome in patients with elevated white cell counts.
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Affiliation(s)
| | | | - Muhammad Imran
- Pathology/Histopathology, Allama Iqbal Medical College, Lahore, PAK
| | | | - Ahmadullah Baig
- Internal Medicine, Allama Iqbal Medical College, Lahore, PAK
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Pan ST, Tseng SP, Wang CH, Chou YT. Paraneoplastic Leukemoid Reaction after Primary Tumor Resection in Patients with Urothelial Carcinoma: A Report of 2 Cases. CLINICAL PATHOLOGY 2021; 14:2632010X211030515. [PMID: 34291205 PMCID: PMC8278444 DOI: 10.1177/2632010x211030515] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Accepted: 06/10/2021] [Indexed: 11/15/2022]
Abstract
Leukemoid reaction (LR), which is defined as leukocytosis with a white blood cell (WBC) count above 50 000/µL, can be caused by various conditions, while paraneoplastic leukemoid reaction (PLR), a rare type of paraneoplastic syndrome, occurs in cases of solid tumors. Here we report 2 cases of high-grade urothelial carcinoma (HGUC) with PLR accompanied by rapid tumor progression after complete resection of the primary tumor. We reviewed the patient’s clinical history, histopathology, and the results of laboratory tests to rule out LR induced by non-tumor causes. In both cases, PLR appeared after primary tumor resection, and the patients died of disease at the peak of PLR at 6 and 8 weeks. Immunohistochemistry for granulocyte colony-stimulating factor and its receptor was performed on tumor tissues. Patients with HGUC and PLR are rare and have an extremely poor prognosis. The mechanism by which solid tumors are associated with PLR and rapid tumor progression after surgical resection of the primary tumor is incompletely understood and will be discussed here.
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Affiliation(s)
- Shien-Tung Pan
- Department of Pathology, Tungs' Taichung MetroHarbor Hospital, Taichung City.,Department of Pathology, China Medical University Hsinchu Hospital, Hsinchu County
| | - Shu-Ping Tseng
- Department of Pathology, Tungs' Taichung MetroHarbor Hospital, Taichung City
| | - Chiou-Huey Wang
- Department of Pathology, Tungs' Taichung MetroHarbor Hospital, Taichung City.,Department of Medical Technology, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli County
| | - Yu-Ting Chou
- Institute of Biotechnology, National Tsing-Hua University, HsinChu City
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Al Sbihi AF, Manasrah N, Al Haj FM, Al Qasem S, Appel J. A Paraneoplastic Leukemoid Reaction in Primary Lung Sarcoma. Cureus 2021; 13:e15047. [PMID: 34150398 PMCID: PMC8203290 DOI: 10.7759/cureus.15047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/04/2022] Open
Abstract
Pulmonary malignancies are known to have high prevalence and mortality. They are associated with different paraneoplastic syndromes, especially pulmonary carcinomas, because they are more common than pulmonary sarcomas. We present a case of a 56-year-old African American male who was admitted to our institution with a three-month history of a dry cough, progressive shortness of breath, and two to three days of right arm swelling. He had extreme leukocytosis (WBC count of 106,500 cells/mm3). Computed tomography (CT) scan of the thorax demonstrated an irregular, thick-walled 14-cm lung mass occupying the middle and upper hemithorax. CT-guided biopsy of the mass confirmed the diagnosis of lung sarcoma.
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Affiliation(s)
- Ali F Al Sbihi
- Internal Medicine, DMC (Detroit Medical Center) Sinai-Grace Hospital, Detroit, USA
| | - Nouraldeen Manasrah
- Internal Medicine, DMC (Detroit Medical Center) Sinai-Grace Hospital, Detroit, USA
| | - Farah M Al Haj
- Internal Medicine, Wayne State University Detroit Medical Center, Detroit, USA
| | | | - Joel Appel
- Internal Medicine, DMC (Detroit Medical Center) Sinai-Grace Hospital, Detroit, USA
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Hyperleukocytosis in Solid tumors: A Rare Paraneoplastic Syndrome Associated with Poor Prognosis. Am J Med Sci 2021; 362:211-214. [PMID: 33989562 DOI: 10.1016/j.amjms.2021.01.027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Revised: 10/09/2020] [Accepted: 01/26/2021] [Indexed: 12/24/2022]
Abstract
Hematological paraneoplastic syndromes are fairly uncommon. While mild leukocytosis in solid tumors is well reported, white blood cell (WBC) count over 50,000 u/L, described as paraneoplastic leukemoid reaction (PLR), is not. Indeed, when found, it is usually associated with a higher burden of disease, tumor activity and worse clinical outcomes. We report the case of a challenging and burdensome diagnosis of a presumptive hematological paraneoplastic syndrome in a patient with a locally advanced lung cancer admitted in the Internal Medicine ward. After the end of chemotherapy, clinical and laboratory benefit was observed; however, the aggressive course of the disease became clear, with progression and downhill course that was unresponsive to treatment.
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Abukhiran I, Mott SL, Bellizzi AM, Boukhar SA. Paraneoplastic leukemoid reaction: Case report and review of the literature. Pathol Res Pract 2021; 217:153295. [PMID: 33341546 DOI: 10.1016/j.prp.2020.153295] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Revised: 11/18/2020] [Accepted: 11/20/2020] [Indexed: 11/11/2022]
Abstract
OBJECTIVES We recently encountered a patient with unexplained hyperleukocytosis (105.4 K/μL at presentation), subsequently found to have colon cancer with a marked tumor-associated neutrophilic infiltrate; the leukocytosis abruptly improved after tumor removal. Paraneoplastic leukemoid reaction (PLR) is a rare entity, occurring due to tumor cytokine secretion (typically granulocyte-colony stimulating factor [G-CSF]). We describe a case and aggregate results of previously published cases. METHODS We reviewed the English-language literature for all prior reports of PLR, recording age, gender, histologic diagnosis, WBC count, G-CSF level, and overall survival. We analyzed clinicopathologic variables' impact on survival. RESULTS We identified 179 cases (mean age 64; 72 % M). Adeno-, squamous cell, sarcomatoid, and undifferentiated carcinomas accounted for >70 %. Esophagus, gallbladder, lung, liver, and pancreas were the most common primaries. At time of publication 81 % of patients had died, with mean overall survival of 4 months. There was no correlation between WBC count and G-CSF level. On univariate analysis, WBC count was the only variable associated with survival (P = 0.03). Patients with WBC counts >100 K/μL were twice as likely to die as those with counts from 11 K to 40 K/μL. CONCLUSIONS PLR, typically carcinoma-associated, is characterized by dismal prognosis. The WBC count is inversely related to survival. Knowledge of this phenomenon militates against protracted, expensive work ups. In malignant neoplasms with prominent neutrophilic stroma, the pathologist should correlate with the WBC count and, if markedly elevated (>40 K/μL), raise consideration for PLR.
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Affiliation(s)
- Ibrahim Abukhiran
- Department of Pathology, University of Iowa Hospitals and Clinics and Carver College of Medicine, Iowa City, IA, USA
| | - Sarah L Mott
- Holden Comprehensive Cancer Center, University of Iowa Hospitals and Clinics and Carver College of Medicine, Iowa City, IA, USA
| | - Andrew M Bellizzi
- Department of Pathology, University of Iowa Hospitals and Clinics and Carver College of Medicine, Iowa City, IA, USA.
| | - Sarag A Boukhar
- Department of Pathology, University of Iowa Hospitals and Clinics and Carver College of Medicine, Iowa City, IA, USA.
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8
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Azzam O, Hewavitharana CH, Fermoyle S, Prentice D. Paraneoplastic leukemoid reaction in a localised squamous cell oesophageal cancer with paracrine G-CSF production. BMJ Case Rep 2020; 13:13/10/e235069. [PMID: 33040032 PMCID: PMC7552795 DOI: 10.1136/bcr-2020-235069] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
A 51-year-old-man presented with symptoms and baseline investigations suggestive of an infective process. Most strikingly, there was a pronounced neutrophil predominant leucocytosis. Lack of a clinical and biochemical response to empirical antibiotic therapy, prompted imaging for a deep-seated infective process, incidentally uncovering a gastro-oesophageal junction tumour. Resection of the tumour was followed by rapid resolution of the leucocytosis. He remains in clinical remission since tumour resection and adjuvant chemotherapy. Cancer-associated leukemoid reactions in non-disseminated tumours are rare. The role of polymorphonuclear (PMN) leucocytes both in the peripheral blood and the tumour itself is discussed herein. There is increasing recognition of the importance of the non-cancer cellular components of the tumour microenvironment. Myeloid suppressor cells are a subset of PMN leucocytes which play a role in tumour progression.The role of these cells and granulocyte colony-stimulating factor is highlighted in this case.
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Affiliation(s)
- Omar Azzam
- Internal Medicine, Royal Perth Hospital, Perth, Western Australia, Australia
| | | | - Soraya Fermoyle
- Department of Anatomical Pathology, Fiona Stanley Hospital, Murdoch, Western Australia, Australia
| | - David Prentice
- Internal Medicine, Royal Perth Hospital, Perth, Western Australia, Australia
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Kabashneh S, Ali H, Shanah L, Alkofahi AA, Alkassis S. Paraneoplastic Leukocytosis: A Poor Prognostic Marker in Pancreatic Adenocarcinoma. Cureus 2020; 12:e9013. [PMID: 32775093 PMCID: PMC7405973 DOI: 10.7759/cureus.9013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/02/2022] Open
Abstract
Hyperleukocytosis is a rare form of paraneoplastic syndrome that has been reported in adenocarcinomas, particularly pancreatic cancer. We present an elderly man with chronic abdominal pain and weight loss for six months. On examination, he had diffuse tenderness and marked ascites. A workup with a CT scan revealed a pancreatic mass, which was confirmed to be pancreatic adenocarcinoma on biopsy. His lab work showed a significant leukocytosis. An extensive infectious workup was negative. He was not on any medications known to cause a leukocytosis; therefore, his leukocytosis was attributed to his cancer. Unfortunately, he died just a few days later. This case highlights hyperleukocytosis as a paraneoplastic syndrome that is a poor prognostic sign, and can be used as a marker for disease progression.
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Chang KWL, Kwok LL, Rana MK, Patel S, Birris T. Paraneoplastic Leukemoid Reaction in Gastroesophageal Junction Adenocarcinoma: A Case Report. AMERICAN JOURNAL OF CASE REPORTS 2020; 21:e919596. [PMID: 32001665 PMCID: PMC7011169 DOI: 10.12659/ajcr.919596] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
BACKGROUND The presence of leukocytosis associated with non-hematological malignancy after ruling out other causes is defined as paraneoplastic leukemoid reaction (PLR). PLR is a rare manifestation of various solid tumors. It is associated with poor prognosis unless receiving effective antineoplastic treatments. CASE REPORT A 72-year-old female was referred to a hematologist/oncologist for the evaluation of leukocytosis with neutrophilia. Initial workup was unremarkable; however, she had progressively worsening leukocytosis with neutrophilia, associated with severe anemia and dysphagia. Computed tomography (CT) scan revealed wall thickening at the gastroesophageal junction (GEJ) and multiple hypodensities of the liver. Esophagogastroduodenoscopy (EGD) confirmed the diagnosis of GEJ tumor and biopsy returned as adenocarcinoma with human epidermal growth factor receptor 2 (HER2) overexpression. Leukocytosis resolved after the first round of chemotherapy and the patient remains progression-free with the addition of trastuzumab to her chemotherapy regimen. CONCLUSIONS We report a rare case of PLR caused by GEJ adenocarcinoma. This is the first case of PLR in a patient with metastatic GEJ adenocarcinoma with HER2 overexpression in the Caucasian population. It is important to workup leukocytosis promptly, to keep malignancy in the differential diagnosis and to seek early hematology/oncology consultation.
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Affiliation(s)
| | - Lai Lai Kwok
- Department of Family Medicine, Spectrum Health Lakeland, Saint Joseph, MI, USA
| | - Manish K Rana
- Department of Graduate Medical Education, Spectrum Health Lakeland, Saint Joseph, MI, USA
| | - Sapna Patel
- Department of Hematology and Oncology, Spectrum Health Lakeland, Saint Joseph, MI, USA
| | - Thomas Birris
- Department of Gastroenterology, Spectrum Health Lakeland , Saint Joseph, MI, USA
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Xing Z, Scott B. Severe Leukemoid Reaction in a Case of Soft Tissue Sarcoma: A Case Report. JBJS Case Connect 2019; 9:e0368. [PMID: 31592819 DOI: 10.2106/jbjs.cc.18.00368] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
CASE A 62-year-old woman presented with severe leukocytosis and systemic symptoms including fatigue, low appetite, and weight loss. After 4 months of evaluation by doctors with extensive laboratory tests and imaging studies, a soft tissue sarcoma in the left posterior distal thigh was revealed. Quickly after surgical excision of the soft tissue sarcoma, the leukocytosis and systemic symptoms were dramatically resolved. CONCLUSIONS Leukemoid reaction can present as a paraneoplastic syndrome. Awareness of soft tissue sarcoma as a possible cause of leukemoid reaction may help improve the early diagnosis and subsequent early intervention in future cases.
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12
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Hu B, Sang XT, Yang XB. Paraneoplastic leukemoid reaction in a patient with sarcomatoid hepatocellular carcinoma: A case report. World J Clin Cases 2019; 7:1330-1336. [PMID: 31236397 PMCID: PMC6580346 DOI: 10.12998/wjcc.v7.i11.1330] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2019] [Revised: 04/02/2019] [Accepted: 04/19/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Sarcomatoid hepatocellular carcinoma (SHC) combined with paraneoplastic leukemoid reaction (PLR), which is associated with a poor prognosis, is rarely seen in the clinic. Here, we report the case of a patient in the above situation.
CASE SUMMARY A 75-year-old female patient with a past medical history of hypertension and cerebral infarction paid a hospital visit as a result of right upper quadrant abdominal pain and anorexia for two months. Laboratory examination revealed a white blood cell (WBC) count of 43790/μL, which was then increased up to 77050/μL. In addition, the results of bone marrow examination suggested a leukemoid reaction. Computed tomography (CT) revealed a focal hepatic mass, which was confirmed through pathological examination to be an SHC postoperatively. In addition, the WBC count had fallen to a normal level before she left the hospital. However, the patient died two and a half months after the second hospital admission.
CONCLUSION This is a rare case of SHC combined with PLR, both of which have an extremely poor prognosis.
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Affiliation(s)
- Bo Hu
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Xin-Ting Sang
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Xiao-Bo Yang
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
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Paraneoplastic syndromes in cancers of unknown primary: An unknown field for oncologists. Bull Cancer 2019; 106:590-603. [DOI: 10.1016/j.bulcan.2019.03.011] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2018] [Revised: 02/21/2019] [Accepted: 03/08/2019] [Indexed: 12/11/2022]
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Yu G, Ji H, Meng C, Huang Y, Gao G, Liu C, Wang S, Zhang L, Ju J. Esophageal adenocarcinoma with leukemoid reaction: a case report. J Cardiothorac Surg 2019; 14:66. [PMID: 30961609 PMCID: PMC6454710 DOI: 10.1186/s13019-019-0893-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2019] [Accepted: 04/01/2019] [Indexed: 11/11/2022] Open
Abstract
Background Leukemoid reaction (LR) is defined as a reactive leucocytosis with WBC counts exceeding 50,000/mm3, and a significant increase in early neutrophil precursors. LR may be a paraneoplastic manifestation of various malignant tumors. Tumor-related LR is a kind of neoplastic syndrome, unrelated to an infection or other diseases. Case presentation A 74-year-old male visited a local doctor with a 20-day history of progressive dysphagia. The complete blood count revealed leucocytosis. Bone marrow aspirates and a biopsy confirmed LR and excluded chronic myelogenous leukemia. Following radical esophagectomy for an adenocarcinoma the WBC counts successively decreased to 10,450/mm3 and 8670/mm3 within 1 week and 1 month, respectively. Conclusion We report a rare case of esophageal adenocarcinoma complicated with excessive leucocytosis caused by paraneoplastic LR; we also present a review of literature and an investigation of the clinical features. To our knowledge, this is the first report of LR associated with esophageal adenocarcinoma.
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Affiliation(s)
- Ge Yu
- Department of Thoracic Surgery, Weihai Municipal Hospital, 70 Heping Road, Weihai, 264200, Shandong, China
| | - Huaijun Ji
- Department of Thoracic Surgery, Weihai Municipal Hospital, 70 Heping Road, Weihai, 264200, Shandong, China.
| | - Chuizheng Meng
- Department of Thoracic Surgery, Weihai Municipal Hospital, 70 Heping Road, Weihai, 264200, Shandong, China
| | - Yixuan Huang
- Department of Thoracic Surgery, Weihai Municipal Hospital, 70 Heping Road, Weihai, 264200, Shandong, China
| | - Guogang Gao
- Department of Thoracic Surgery, Weihai Municipal Hospital, 70 Heping Road, Weihai, 264200, Shandong, China
| | - Chuanping Liu
- Department of Thoracic Surgery, Weihai Municipal Hospital, 70 Heping Road, Weihai, 264200, Shandong, China
| | - Shanlei Wang
- Department of Thoracic Surgery, Weihai Municipal Hospital, 70 Heping Road, Weihai, 264200, Shandong, China
| | - Lei Zhang
- Department of Thoracic Surgery, Weihai Municipal Hospital, 70 Heping Road, Weihai, 264200, Shandong, China
| | - Jin Ju
- Department of Thoracic Surgery, Weihai Municipal Hospital, 70 Heping Road, Weihai, 264200, Shandong, China.
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Vallianou NG, Margellou E, Kounatidis D, Dolapsakis C, Magkou C. Fever and Leukemoid Reaction as the Presenting Manifestation of Disseminated Parotid Gland Carcinoma. Am J Med Sci 2019; 357:517-518. [PMID: 30846188 DOI: 10.1016/j.amjms.2019.01.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2018] [Revised: 01/18/2019] [Accepted: 01/29/2019] [Indexed: 11/11/2022]
Affiliation(s)
| | | | | | | | - Christina Magkou
- Pathology Department, Evangelismos General Hospital, Athens, Greece
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Negri L, Ferrara N. The Prokineticins: Neuromodulators and Mediators of Inflammation and Myeloid Cell-Dependent Angiogenesis. Physiol Rev 2018. [PMID: 29537336 DOI: 10.1152/physrev.00012.2017] [Citation(s) in RCA: 73] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
The mammalian prokineticins family comprises two conserved proteins, EG-VEGF/PROK1 and Bv8/PROK2, and their two highly related G protein-coupled receptors, PKR1 and PKR2. This signaling system has been linked to several important biological functions, including gastrointestinal tract motility, regulation of circadian rhythms, neurogenesis, angiogenesis and cancer progression, hematopoiesis, and nociception. Mutations in PKR2 or Bv8/PROK2 have been associated with Kallmann syndrome, a developmental disorder characterized by defective olfactory bulb neurogenesis, impaired development of gonadotropin-releasing hormone neurons, and infertility. Also, Bv8/PROK2 is strongly upregulated in neutrophils and other inflammatory cells in response to granulocyte-colony stimulating factor or other myeloid growth factors and functions as a pronociceptive mediator in inflamed tissues as well as a regulator of myeloid cell-dependent tumor angiogenesis. Bv8/PROK2 has been also implicated in neuropathic pain. Anti-Bv8/PROK2 antibodies or small molecule PKR inhibitors ameliorate pain arising from tissue injury and inhibit angiogenesis and inflammation associated with tumors or some autoimmune disorders.
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Affiliation(s)
- Lucia Negri
- Sapienza University of Rome, Rome, Italy ; and University of California, San Diego, La Jolla, California
| | - Napoleone Ferrara
- Sapienza University of Rome, Rome, Italy ; and University of California, San Diego, La Jolla, California
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Åström M, Tajeddinn W, Karlsson MG, Linder O, Palmblad J, Lindblad P. Cytokine Measurements for Diagnosing and Characterizing Leukemoid Reactions and Immunohistochemical Validation of a Granulocyte Colony-Stimulating Factor and CXCL8-Producing Renal Cell Carcinoma. Biomark Insights 2018; 13:1177271918792246. [PMID: 30147294 PMCID: PMC6100120 DOI: 10.1177/1177271918792246] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2018] [Accepted: 07/11/2018] [Indexed: 12/17/2022] Open
Abstract
Background Various paraneoplastic syndromes are encountered in renal cell carcinomas. This case report illustrates that a paraneoplastic leukemoid reaction may precede the diagnosis of renal cell carcinoma and be explained by cytokine production from the cancer cells. Case presentations A 64-year-old man was referred for hematology workup due to pronounced leukocytosis. While being evaluated for a possible hematologic malignancy as the cause, he was found to have a metastasized renal cell carcinoma, and hyperleukocytosis was classified as a leukemoid reaction. A multiplex panel for measurement of 25 serum cytokines/chemokines showed highly elevated levels of granulocyte colony-stimulating factor (G-CSF) and CXCL8 (C-X-C-motif chemokine ligand 8, previously known as interleukin [IL]-8). By immunohistochemistry it was shown that the renal carcinoma cells expressed both these cytokines. Two additional, consecutive patients with renal cell carcinoma with paraneoplastic leukocytosis also showed elevated serum levels of CXCL8, but not of G-CSF. Nonparametric statistical evaluation showed significantly higher serum concentrations of CXCL8, IL-6, IL-10, monocyte chemoattractant protein 1 (MCP-1), and tumor necrosis factor, but lower interferon gamma (IFN-γ) and IL-1α, for the 3 renal cell carcinoma cases compared with healthy blood donors. Conclusions In suspected paraneoplastic leukocytosis, multiplex serum cytokine analyses may facilitate diagnosis and provide an understanding of the mechanisms for the reaction. In the index patient, combined G-CSF and CXCL8 protein expression by renal carcinoma cells was uniquely documented. A rapidly fatal course was detected in all 3 cases, congruent with the concept that autocrine/paracrine growth signaling in renal carcinoma cells may induce an aggressive tumor phenotype. Immune profiling studies could improve our understanding for possible targets when choosing therapies for patients with metastatic renal cell carcinoma.
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Affiliation(s)
- Maria Åström
- Division of Hematology, Department of Medicine, Örebro University Hospital, Örebro, Sweden.,Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.,iRiSC - Inflammatory Response and Infection Susceptibility Centre, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Walid Tajeddinn
- iRiSC - Inflammatory Response and Infection Susceptibility Centre, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Mats G Karlsson
- Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Olle Linder
- Division of Hematology, Department of Medicine, Örebro University Hospital, Örebro, Sweden
| | - Jan Palmblad
- Division of Hematology, Department of Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden
| | - Per Lindblad
- Department of Urology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
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18
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Sakr R, Renneville A, Saada V, Cotteret S, Martin JE, Droin N, Selimoglu-Buet D, Besse B, Hollebecque A, Marzac C, Pasquier F, Micol JB, De Botton S, Mir O, Solary E, Willekens C. Next-generation sequencing discriminates myelodysplastic/myeloproliferative neoplasms from paraneoplastic leukemoid reaction in cancer patients with hyperleukocytosis. Leuk Lymphoma 2017; 59:1742-1745. [DOI: 10.1080/10428194.2017.1397669] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Affiliation(s)
- Riwa Sakr
- Département d’Hématologie, Gustave Roussy, Université Paris-Saclay, Villejuif, France
| | - Aline Renneville
- Centre de Biologie et Pathologie, Laboratoire d’hématologie, Centre Hospitalier Universitaire (CHU) Lille, Lille, France
| | - Veronique Saada
- Département de Biologie-Pathologie, Laboratoire d’hématologie, Gustave Roussy, Université Paris-Saclay, Villejuif, France
| | - Sophie Cotteret
- Département de Biologie-Pathologie, Laboratoire de cytogénétique, Gustave Roussy, Université Paris-Saclay, Villejuif, France
| | - Jean-Edouard Martin
- Département d’Hématologie, Gustave Roussy, Université Paris-Saclay, Villejuif, France
| | | | | | - Benjamin Besse
- Département de Médecine Oncologique, Gustave Roussy, Université Paris-Saclay, Villejuif, France
| | - Antoine Hollebecque
- Département de Médecine Oncologique, Gustave Roussy, Université Paris-Saclay, Villejuif, France
| | - Christophe Marzac
- Département de Biologie-Pathologie, Laboratoire d’hématologie, Gustave Roussy, Université Paris-Saclay, Villejuif, France
| | - Florence Pasquier
- Département d’Hématologie, Gustave Roussy, Université Paris-Saclay, Villejuif, France
| | - Jean-Baptiste Micol
- Département d’Hématologie, Gustave Roussy, Université Paris-Saclay, Villejuif, France
| | - Stéphane De Botton
- Département d’Hématologie, Gustave Roussy, Université Paris-Saclay, Villejuif, France
- INSERM U1170, Gustave Roussy, Villejuif, France
- Faculté de Médecine, Université Paris-Sud, Le Kremlin-Bicêtre, France
| | - Olivier Mir
- Département de Médecine Oncologique, Gustave Roussy, Université Paris-Saclay, Villejuif, France
| | - Eric Solary
- Département d’Hématologie, Gustave Roussy, Université Paris-Saclay, Villejuif, France
- INSERM U1170, Gustave Roussy, Villejuif, France
- Faculté de Médecine, Université Paris-Sud, Le Kremlin-Bicêtre, France
| | - Christophe Willekens
- Département d’Hématologie, Gustave Roussy, Université Paris-Saclay, Villejuif, France
- INSERM U1170, Gustave Roussy, Villejuif, France
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Matsumoto Y, Mabuchi S, Kozasa K, Kuroda H, Sasano T, Yokoi E, Komura N, Sawada K, Kimura T. The significance of tumor-associated neutrophil density in uterine cervical cancer treated with definitive radiotherapy. Gynecol Oncol 2017; 145:469-475. [DOI: 10.1016/j.ygyno.2017.02.009] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2016] [Revised: 02/02/2017] [Accepted: 02/04/2017] [Indexed: 12/11/2022]
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20
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[Hyperleucocytosis with acute uric acid nephropathy in a patient with hepatocellular carcinoma]. Presse Med 2017; 46:238-239. [PMID: 28087209 DOI: 10.1016/j.lpm.2016.11.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2016] [Revised: 09/24/2016] [Accepted: 11/21/2016] [Indexed: 11/20/2022] Open
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21
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Liang W, Ferrara N. The Complex Role of Neutrophils in Tumor Angiogenesis and Metastasis. Cancer Immunol Res 2016; 4:83-91. [PMID: 26839309 DOI: 10.1158/2326-6066.cir-15-0313] [Citation(s) in RCA: 264] [Impact Index Per Article: 29.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Chronic inflammation fosters cancer development and progression and also modulates tumor responses to anticancer therapies. Neutrophils are key effector cells in innate immunity and are known to play a critical role in various inflammatory disorders. However, the functions of neutrophils in cancer pathogenesis have been largely neglected until recently and still remain poorly characterized compared with other immune cells in the tumor microenvironment. We highlight recent findings on the mechanisms by which tumor cells, in cooperation with tumor-associated stromal cells, induce expansion, recruitment, and polarization of neutrophils. We also review the multifaceted roles that neutrophils play in different aspects of cancer development and progression, with an emphasis on tumor angiogenesis and metastasis.
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Affiliation(s)
- Wei Liang
- Moores Cancer Center and Department of Pathology, University of California San Diego, La Jolla, California
| | - Napoleone Ferrara
- Moores Cancer Center and Department of Pathology, University of California San Diego, La Jolla, California.
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22
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McCoach CE, Rogers JG, Dwyre DM, Jonas BA. Paraneoplastic Leukemoid Reaction as a Marker of Tumor Progression in Non-Small Cell Lung Cancer. ACTA ACUST UNITED AC 2015; 4:15-18. [PMID: 25932381 DOI: 10.1016/j.ctrc.2015.03.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Affiliation(s)
- Caroline E McCoach
- Division of Hematology/Oncology, Department of Medicine, University of Colorado School of Medicine, MS 8117, 12801 E 17 Ave, Room 8122, Aurora, CO 80045
| | - Jessica G Rogers
- Department of Medical Pathology and Laboratory Medicine, University of California Davis Medical Center, 4400 V Street, Sacramento, CA 95817
| | - Denis M Dwyre
- Department of Medical Pathology and Laboratory Medicine, University of California Davis Medical Center, 4400 V Street, Sacramento, CA 95817
| | - Brian A Jonas
- Division of Hematology/Oncology, Department of Internal Medicine, University of California Davis Medical Center, 4501 X Street, Suite 3016, Sacramento, CA 95817,
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