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Open Access

Peer-reviewed

Research Article

Pulmonary tumor embolism: A retrospective study over a 30-year period

  • Xin He,

    Roles Data curation, Investigation, Methodology, Writing – original draft

    Affiliations Department of Pathology and Laboratory Medicine, Rhode Island Hospital and The Alpert Medical School of Brown University, Providence, RI, United States of America, Department of Pathology, University of Massachusetts School of Medicine, Worcester, MA, United States of America

    ⨯
  • Douglas C. Anthony,

    Roles Writing – review & editing

    Affiliations Department of Pathology and Laboratory Medicine, Rhode Island Hospital and The Alpert Medical School of Brown University, Providence, RI, United States of America, Department of Neurology, Rhode Island Hospital and The Alpert Medical School of Brown University, Providence, RI, United States of America

    ⨯
  • Zulmira Catoni,

    Roles Data curation

    Affiliation Human Information Management, Rhode Island Hospital and The Alpert Medical School of Brown University, Providence, RI, United States of America

    ⨯
  • Weibiao Cao

    Roles Conceptualization, Formal analysis, Investigation, Methodology, Project administration, Writing – original draft, Writing – review & editing

    Weibiao_Cao@alumni.brown.edu

    Affiliations Department of Pathology and Laboratory Medicine, Rhode Island Hospital and The Alpert Medical School of Brown University, Providence, RI, United States of America, Department of Medicine, Rhode Island Hospital and The Alpert Medical School of Brown University, Providence, RI, United States of America

    ⨯

Abstract

Background

Pulmonary tumor embolism (PTE) is difficult to detect before death, and it is unclear whether the discrepancy between antemortem clinical and postmortem diagnosis improves with the advance of the diagnostic technologies. In this study we determined the incidence of PTE and analyzed the discrepancy between antemortem clinical and postmortem diagnosis.

Methods

We performed a retrospective autopsy study on patients with the history of malignant solid tumors from 1990 to 2020 and reviewed all the slides of the patients with PTE. We also analyzed the discrepancies between antemortem clinical and postmortem diagnosis in 1999, 2009 and 2019 by using the Goldman criteria. Goldman category major 1 refers to cases in which an autopsy diagnosis was the direct cause of death and was not recognized clinically, but if it had been recognized, it may have changed treatment or prolonged survival.

Results

We found 20 (3%) cases with PTE out of the 658 autopsy cases with solid malignancies. Out of these 20 cases, urothelial carcinoma (30%, 6/20) and invasive ductal carcinoma of the breast (4/20, 20%) were the most common primary malignancies. Seven patients with shortness of breath died within 3–17 days (average 8.4±2.2 days) after onset of the symptoms. Pulmonary embolism was clinically suspected in seven out of twenty (35%, 7/20) patients before death, but only two patients (10, 2/20) were diagnosed by imaging studies before death. The rate of Goldman category major 1 was 13.2% (10/76) in 1999, 7.3% (4/55) in 2009 and 6.9% (8/116) in 2019. Although the rate of Goldman category major 1 appeared decreasing, the difference was not statistically significant. The autopsy rate was significantly higher in 2019 (8.4%, 116/1386) than in 2009 (4.4%, 55/1240).

Conclusions

The incidence of PTE is uncommon. Despite the advances of the radiological techniques, radiological imaging studies did not detect the majority of PTEs. The discrepancy between the antemortem clinical and the postmortem diagnosis has not improved significantly over the past 30 years, emphasizing the value of autopsy.

Citation: He X, Anthony DC, Catoni Z, Cao W (2021) Pulmonary tumor embolism: A retrospective study over a 30-year period. PLoS ONE 16(8): e0255917. https://doi.org/10.1371/journal.pone.0255917

Editor: Xuan-Zheng Shi, University of Texas Medical Branch, UNITED STATES

Received: March 24, 2021; Accepted: July 26, 2021; Published: August 11, 2021

Copyright: © 2021 He et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the paper.

Funding: The author(s) received no specific funding for this work.

Competing interests: No authors have competing interests.

Abbreviations: PTE, pulmonary tumor embolism; ED, Emergency Department

Introduction

Pulmonary tumor embolism is characterized by emboli in the pulmonary arterial system (including alveolar septal capillaries) consisting of tumor cells without fibrocellular intimal proliferation and not contiguous with the metastatic foci [1]. It is a rare event in the late stages of malignancy that carries a poor prognosis. Occlusion of the pulmonary microvasculature by tumor cells and associated thrombi may mimic thromboembolic disease. Detection of tumor cells in pulmonary vessels within the lung specimens is the only means to establish diagnosis. Unfortunately, microscopic pulmonary tumor embolism is rarely recognized before death [2] since 1) the clinical features of PTE are quite similar to those of thrombotic pulmonary embolism; 2) the difference between thrombotic and metastatic pulmonary embolism is not easily differentiated on radiographic studies, making radiological diagnosis difficult; and 3) PET/CT is not sensitive enough to differentiate tumor embolism from thrombotic embolism [3]. Therefore, pulmonary tumor embolism cases were identified primarily by autopsy.

Dr. Goldman evaluated the discrepancy between the antemortem clinical and autopsy diagnosis in 1983 [4] and proposed five categories. Dr. O’Connor and colleagues modified the classification in 2002 [5]. Category Major 1 refers to cases in which an autopsy diagnosis was the direct cause of death and was not recognized clinically, but if it had been recognized, it may have changed treatment or prolonged survival. The rate of category major 1 was 10% in Dr. Goldman’s study in 1983. It is not clear whether the discrepancy between the antemortem clinical and autopsy diagnosis improves over the past 30 years.

In this study, we performed a retrospective study to determine the incidence and origins of metastatic solid tumors leading to pulmonary tumor embolism over a 30-year period. We reported 20 cases with pulmonary tumor embolism and found that the incidence of pulmonary tumor embolism was 3% in our institution. We also analyzed the discrepancies between the antemortem clinical and the autopsy diagnosis in 1999, 2009 and 2019. The rate of Goldman category major 1 ranged from 6.9% to 13.2%.

Methods

Study design for pulmonary tumor embolism

The institutional review board (IRB) at Rhode Island Hospital approved this study (IRB committee number 1188347). No additional informed consent was required by the IRB for this chart review retrospective study.

This retrospective study consisted of a chart review of autopsies at Rhode Island Hospital from 1990 to 2020. We reviewed autopsy cases with the history of malignant solid tumors (sarcomas, carcinomas, melanomas and lymphomas) and identified cases with pulmonary tumor embolism. The slides of lungs were re-reviewed to confirm the diagnosis of pulmonary tumor embolism. Pertinent clinical and pathologic data for pulmonary tumor embolism cases were collected (Fig 1).

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Fig 1. Flowchart of 658 autopsies with malignant solid tumors in our institution.

https://doi.org/10.1371/journal.pone.0255917.g001

Pulmonary tumor thrombotic microangiopathy is excluded from this study. Pulmonary tumor thrombotic microangiopathy is a related but different entity from pulmonary tumor embolism and is characterized by microscopic tumor cell emboli in the pulmonary microvasculature causing intimal proliferation and a syndrome of hypoxemia, pulmonary hypertension, right heart failure and death [6].

Study design for discrepancies between antemortem clinical and autopsy diagnosis

In order to evaluate the agreement between antemortem clinical and autopsy diagnosis and to analyze how autopsy rate changed over the past 30 years, we reviewed the autopsy reports and the clinical histories of autopsy cases performed at Rhode Island Hospital in 1999, 2009 and 2019. Brain donation (most often for neurodegenerative disease) and medical examiner office cases were excluded. Discrepancies between antemortem clinical and autopsy diagnoses were classified using the modified Goldman criteria [5]. The total, inpatient and emergency department autopsy rates were also calculated.

Statistical analysis

A Chi-square test was utilized to compare groups where appropriate.

Results

Pulmonary tumor embolism in autopsy cases with the history of malignant solid tumors in our institution

We identified 658 autopsy cases with postmortem diagnoses of malignant solid tumors in a period of 30 years from 1990 to 2020. Of the 658 autopsy cases, we found that 20 (3%) cases had pulmonary tumor emboli, including 11 males and 9 females. The average age at death for these 20 cases was 60.5±13 years (range 35–85 years). All cases were stage IV diseases with multiple distant organ metastases, including liver (70%, 14/20), lungs (70%, 14/20), bone (35%, 7/20), gastrointestinal tracts (25%, 5/20), omentum (20%, 4/20), adrenal glands (15%, 3/20), or others. Only one patient was on palliative chemotherapy before death. Two out of the twenty patients had a past medical history of thrombotic events. One patient had lower extremity thrombosis and the other had both lower extremity thrombosis and pulmonary embolism.

Of the 20 cases, urothelial carcinoma (n = 6, 30%) and invasive ductal carcinoma of the breast (n = 4, 20%) were the most common primary malignancies overall (Table 1), whereas in male patients urothelial carcinoma and gastric adenocarcinoma were the most common primaries and in female patients invasive ductal carcinoma of the breast and urothelial carcinoma of the bladder are the most common (Table 1). In addition, we analyzed the difference of primary tumors between the first 15 years (before 2005) and the second 15 years (after 2005). Urothelial carcinoma and colorectal adenocarcinoma were the most common primaries before 2005, whereas invasive ductal carcinoma of the breast and urothelial carcinoma of the bladder were the most common primaries in 2005 and after (Table 2).

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Table 1. Primary malignancies in autopsy cases with pulmonary tumor embolism.

https://doi.org/10.1371/journal.pone.0255917.t001

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Table 2. Comparison of primary malignancies between before and after 2005.

https://doi.org/10.1371/journal.pone.0255917.t002

In 7 out of 20 (35%) patients with symptoms such as shortness of breath, hypoxemia and chest pain and clinically suspected of having pulmonary embolism before death, only one (5%) case was confirmed by imaging. In this case, postmortem gross examination demonstrated pulmonary emboli. Another patient without known symptoms had macroscopic tumor emboli detected by imaging studies and died suddenly. Therefore, the detection rate of pulmonary tumor embolism by the imaging studies was 10% (2/20) in our cohort. Eighteen out of twenty cases (90%, 18/20) only had microscopic pulmonary tumor emboli. For example, a 53-year-old female with history of breast cancer had microscopic pulmonary tumor emboli, which were not detected grossly or by imaging studies (Fig 2).

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Fig 2. Representative case with microscopically but not grossly or radiologically detectable pulmonary tumor embolism in a patient with breast cancer.

A. Radiographic image; B & C. Gross image of the lung; D. H&E image of the lung shows tumor emboli (arrows).

https://doi.org/10.1371/journal.pone.0255917.g002

A majority (60%, 12 of 20) of the patients with pulmonary tumor embolism had no shortness of breath and/or hypoxemia. Among these patients, only microscopic but not macroscopic tumor emboli were found on autopsy. In 7 patients (35%, 7 of 20) with symptoms of shortness of breath and/or hypoxemia, 6 of them (85.7%, 6/7) had only microscopic pulmonary tumor emboli. These 7 patients died within 3–17 days (average 8.4±2.2 days) after the onset of shortness of breath.

These data indicate that the majority of pulmonary tumor emboli are not detectable by imaging and those with shortness of breath and/or hypoxemia died within days after symptom onset.

Discrepancies between antemortem clinical and autopsy diagnoses in our institution

With the advances of technology in imaging, we studied whether the discrepancy between antemortem clinical and autopsy diagnosis improved over time. The percentage of Goldman category major 1 was 13.2% (10/76) in 1999, 7.3% (4/55) in 2009 and 6.9% (8/116) in 2019 (Table 3). Although the percentage appeared to be decreasing, the difference was not statistically significant.

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Table 3. Goldman agreement classification between antemortem clinical diagnosis and autopsy diagnosis in 1999, 2009 and 2019.

https://doi.org/10.1371/journal.pone.0255917.t003

We also analyzed the autopsy rate in 1999, 2009 and 2019. We found that the autopsy rate was 6.4% (76/1194) in 1999, 4.4% (55/1240) in 2009 and 8.4% (116/1386) in 2019. The autopsy rate was significantly decreased in 2009 compared with 1999 and significantly increased in 2019 when compared with 2009, but there was no significant difference between 1999 and 2019 (Fig 3A). We also analyzed the inpatient autopsy rate and the emergency department (ED) autopsy rate to determine whether either site was contributing more to the changes in autopsy rate over time. The inpatient autopsy rate was 7.1% (64/906) in 1999, 4.8% (46/958) in 2009 and 8.3% (86/1041) in 2019. Similar to the overall autopsy rate, the inpatient autopsy rate was significantly decreased in 2009 when compared with 1999 and significantly increased in 2019 when compared with 2009, but there was no significant difference between 1999 and 2019 (Fig 3B). The ED autopsy rate was 4.2% (12/288) in 1999, 3.2% (9/282) in 2009, and 8.4% (30/345) in 2019. The ED autopsy rate was significantly increased in 2019 when compared with 2009, but there was no significant difference between 1999 and 2019 (Fig 3C). These data suggest that the autopsy rate increase in 2019 was due to an increase in both the autopsy rate of the inpatients and that of the ED patients.

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Fig 3. Autopsy rate in 1999, 2009 and 2019.

A. The autopsy rate was significantly decreased in 2009 when compared with 1999 and significantly increased in 2019 when compared with 2009, but there was no significant difference between 1999 and 2019. B. The inpatient autopsy rate was significantly decreased in 2009 when compared with 1999 and significantly increased in 2019 when compared with 2009, but there was no significant difference between 1999 and 2019. C. The ED autopsy rate was significantly increased in 2019 when compared with 2009, but there was no significant difference between 1999 and 2019. These data demonstrate that the autopsy rate increase in 2019 was due to an increase of autopsy rate in both inpatients and ED patients.

https://doi.org/10.1371/journal.pone.0255917.g003

Discussion

The incidence of pulmonary tumor embolism was 3% in our institution, which was slightly lower than that seen in literature which ranged from 3 to 26% of the autopsies in patients with solid tumors [2, 3, 7, 8]. The differences in the incidence could be due to the sampling, as most pulmonary tumor emboli are microscopic, and the more sections taken from the lungs, the higher the incidence of emboli are likely to be found. This study was a retrospective study, and we routinely take one section per lung lobe (at least 5 sections per case). Some prior papers, especially with prospective sampling, may perform greater sampling of the lungs.

Pulmonary tumor embolism may present with a wide range of symptoms, including acute hypoxia, chest and abdominal pain, cough, and indolent pulmonary hypertension [2]. In our institution, 60% (12/20) of the patients with pulmonary tumor embolism had no shortness of breath and/or hypoxemia; 35% (7/20) of patients had symptoms of shortness of breath and/or hypoxemia and died within 3–17 days (average 8.4±2.2 days) after the onset of shortness of breath.

Urothelial carcinoma was one of the most common primary malignancies in both male and female patients. Perhaps this is related to the fact that Rhode Island has the highest incidence of urothelial carcinoma in the United States [9].

To further gather the information about pulmonary tumor embolism, we performed an extensive literature review. Since our study focused on pulmonary tumor embolism in the autopsy cases, we searched PubMed from 1990 to 2020 by using key words “pulmonary tumor embolism and autopsy” and found 238 papers. Among these papers, 84 papers were related to pulmonary tumor embolism (Fig 4). Three papers were excluded, including two pediatric case reports [10, 11] as our study focused on adults, and one paper without primary tumor information [12]. The same authors of the latter [12] published two additional papers which were included in this study. Within 81 papers included, 78 were case reports and 3 were case series (7 to 19 cases).

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Fig 4. Flowchart of the literature review from 1990 to 2020.

https://doi.org/10.1371/journal.pone.0255917.g004

In total, 120 cases with pulmonary tumor embolism were reported in the literature from 1990 to 2020 (Table 4). The most common primaries were breast cancer (14.2%, 17/120), gastric cancer (13.3%, 16/120), hepatocellular carcinoma (12.5%, 15/120), esophageal squamous cell carcinoma (7.5%, 9/120), lung cancer (5.8%, 7/120), urothelial carcinoma (5.8%, 7/120) and pancreatic adenocarcinoma (5%, 6/120). Before 2005, the most common primaries were hepatocellular carcinoma, gastric cancer and esophageal squamous cell carcinoma. After 2005, the most common primaries were breast cancer and gastric cancer. There was a regional difference because the majority of gastric cancer cases were from Japan.

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Table 4. Pulmonary tumor embolism cases between 1990 and 2020 in the literature.

https://doi.org/10.1371/journal.pone.0255917.t004

Out of 81 papers, 51 case reports included the results of pre-mortem imaging studies. In 16 of them (31.4%, 16/51) the imaging studies detected pulmonary emboli. The detection rate by the imaging studies was 25.9% (7/27) before 2005, whereas the rate was 37.5% (9/24) after 2005. The difference was not statistically significant.

After combining our cases with those in the literature, the most common primaries were breast cancer (15%, 21/140), gastric cancer (12.8%, 18/140), hepatocellular carcinoma (11.4%, 16/140), urothelial carcinoma (9.3%, 13/140), esophageal squamous cell carcinoma (6.4%, 9/140), lung cancer (5.7%, 8/140) and pancreatic adenocarcinoma (5%, 7/140). Before 2005, the most common primaries were hepatocellular carcinoma, gastric cancer, esophageal squamous cell carcinoma and breast cancer. After 2005, the most common primaries were breast cancer, gastric cancer and urothelial carcinoma (Table 5). The detection rate of pulmonary tumor embolism by imaging was 20% (7/35) before 2005 and 30.6% (11/36) in and after 2005. The difference was not statistically significant (Fig 5). Therefore, autopsy remains the “gold standard” for the diagnosis of pulmonary tumor embolism.

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Fig 5. Detection rate of pulmonary tumor embolism.

After incorporation of our own cases with the literature, the detection rate of pulmonary tumor emboli by the imaging studies was 20% (7/35) before 2005, whereas the rate was 30.6% (11/36) in and after 2005. The difference was not statistically significant (P>0.05).

https://doi.org/10.1371/journal.pone.0255917.g005

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Table 5. Combination of pulmonary tumor embolism cases of our institution with the literature.

https://doi.org/10.1371/journal.pone.0255917.t005

We also analyzed the discrepancies between antemortem clinical and autopsy diagnosis in our cohort by using the modified Goldman criteria [5]. We found that the percentage of Goldman category major 1 showed a tendency toward decreasing, but the difference was not statistically significant. The incidence of category major 1 was 6.9–13.2% in our study over the time period, which is similar to 10% reported in Dr. Goldman’s study in 1983 [4] and 7% in Dr. O’Connor’s study in 2002 [5]. Our data suggest that the percentage of category major 1 of the discrepancies between antemortem clinical and autopsy diagnosis has not changed significantly over the past 30 years.

The autopsy rate in the US and other western nations has decreased. The autopsy rate in academic hospitals is approximately 10%, while many non-teaching hospitals no longer perform autopsies [13, 14]. The autopsy rate at Rhode Island Hospital in 2019 was significantly higher than 2009, likely due to an increase in the rates for both inpatients and ED patients. The increase of autopsy rate may be due to an implementation of EPIC electronic health record system in our hospital in 2015, which requires the clinical team completing the death certificate to answer whether autopsy has been offered.

In conclusion, the majority of pulmonary tumor emboli cannot be detected radiographically and the autopsy remains the “gold standard” for the diagnosis of pulmonary tumor embolism. Although technologies in radiology have improved remarkably over the past 30 years, the discrepancies between antemortem clinical and autopsy diagnosis do not differ significantly.

Acknowledgments

We would like to thank Dr. Yi Cao, a radiologist at Beth Israel Deaconess Hospital, for editing the manuscript.

References

  1. 1. Bassiri AG, Haghighi B, Doyle RL, Berry GJ, Rizk NW. Pulmonary tumor embolism. Am J Respir Crit Care Med. 1997;155(6):2089–95. Epub 1997/06/01. pmid:9196119.
  2. 2. Roberts KE, Hamele-Bena D, Saqi A, Stein CA, Cole RP. Pulmonary tumor embolism: a review of the literature. Am J Med. 2003;115(3):228–32. Epub 2003/08/26. pmid:12935829.
  3. 3. Blanc AL, Jardin C, Faivre JB, Le Rouzic O, Do Cao C, Benhamed L, et al. Pulmonary artery tumour-embolism diagnosed by endobronchial ultrasound-guided transbronchial needle aspiration. Eur Respir J. 2011;38(2):477–9. Epub 2011/08/02. pmid:21804167.
  4. 4. Goldman L, Sayson R, Robbins S, Cohn LH, Bettmann M, Weisberg M. The value of the autopsy in three medical eras. N Engl J Med. 1983;308(17):1000–5. Epub 1983/04/28. pmid:6835306.
  5. 5. O’Connor AE, Parry JT, Richardson DB, Jain S, Herdson PB. A comparison of the antemortem clinical diagnosis and autopsy findings for patients who die in the emergency department. Acad Emerg Med. 2002;9(9):957–9. Epub 2002/09/05. pmid:12208686.
  6. 6. Suffredini DA, Lee JM, Peer CJ, Pratt D, Kleiner DE, Elinoff JM, et al. Pulmonary tumor thrombotic microangiopathy and pulmonary veno-occlusive disease in a woman with cervical cancer treated with cediranib and durvalumab. BMC Pulm Med. 2018;18(1):112. Epub 2018/07/13. pmid:29996818; PubMed Central PMCID: PMC6042377.
  7. 7. Kane RD, Hawkins HK, Miller JA, Noce PS. Microscopic pulmonary tumor emboli associated with dyspnea. Cancer. 1975;36(4):1473–82. Epub 1975/10/01. pmid:1175142.
  8. 8. Winterbauer RH, Elfenbein IB, Ball WC, Jr. Incidence and clinical significance of tumor embolization to the lungs. Am J Med. 1968;45(2):271–90. Epub 1968/08/01. pmid:4299069.
  9. 9. Faricy-Anderson K, Fulton J, Mega A. Why Does Rhode Island Have the Greatest Incidence of Bladder Cancer In the United States? MEDICINE & HEALTH/RHODE ISLAND. 2010;90(10):308–16. pmid:21284270
  10. 10. Fukuda A, Isoda T, Sakamoto N, Nakajima K, Ohta T. Lessons from a patient with cardiac arrest due to massive pulmonary embolism as the initial presentation of Wilms tumor: a case report and literature review. BMC Pediatr. 2019;19(1):39. Epub 2019/02/02. pmid:30704433; PubMed Central PMCID: PMC6354414.
  11. 11. Auger M, Raney B, Callender D, Eifel P, Ordonez NG. Metastatic intracranial chordoma in a child with massive pulmonary tumor emboli. Pediatr Pathol. 1994;14(5):763–70. Epub 1994/09/01. pmid:7808974.
  12. 12. Soares FA, Landell GA, de Oliveira JA. Clinical aspects of tumour involvement of the pulmonary vessels. Acta Oncol. 1992;31(5):519–23. Epub 1992/01/01. pmid:1419097.
  13. 13. Levy B. Informatics and Autopsy Pathology. Surg Pathol Clin. 2015;8(2):159–74. Epub 2015/06/13. pmid:26065791.
  14. 14. Lundberg GD. Low-tech autopsies in the era of high-tech medicine: continued value for quality assurance and patient safety. JAMA. 1998;280(14):1273–4. Epub 1998/10/24. pmid:9786381.
  15. 15. Kiljunen M, Rinta-Kiikka I, Barlund M, Lagerstedt A. [Cancer patient with dyspnoe—remember the possibility of pulmonary tumor microembolism]. Duodecim. 2010;126(18):2147–52. Epub 2010/11/16. pmid:21072962.
  16. 16. Lammi M, Wurzel J, Criner GJ. Pulmonary tumor embolism. Lung. 2010;188(5):441–3. Epub 2010/07/08. pmid:20607269.
  17. 17. Kridel R, Myit S, Pache JC, Gaspoz JM. Pulmonary tumor embolism: a rare cause of acute right heart failure with elevated D-dimers. J Thorac Oncol. 2008;3(12):1482–3. Epub 2008/12/06. pmid:19057276.
  18. 18. Nakamura H, Adachi H, Sudoh A, Yagyu H, Kishi K, Oh-ishi S, et al. Subacute cor pulmonale due to tumor embolism. Intern Med. 2004;43(5):420–2. Epub 2004/06/23. pmid:15206557.
  19. 19. Deeren D, Verbeken E, Vanderschueren S, Wilmer A, Bobbaers H, Meersseman W. Cancer presenting as fatal pulmonary tumour embolism. Acta Clin Belg. 2006;61(1):30–4. Epub 2006/05/06. pmid:16673614.
  20. 20. Vlenterie M, Desar IM, van Herpen CM, Tol J. Fatal microscopic pulmonary tumour embolisms in patients with breast cancer: necessary knowledge for future medical practice. Neth J Med. 2014;72(1):28–31. Epub 2014/01/25. pmid:24457436.
  21. 21. Gajdos C, Nierman DM, Moqtaderi FF, Brower ST, Lento P, Bleiweiss IJ. Microscopic Pulmonary Tumor Emboli: An Unusual Presentation of Breast Cancer. The breast journal. 2000;6(4):273–5. Epub 2001/05/12. pmid:11348379.
  22. 22. Uga S, Ikeda S, Matsukage S, Hamada M. An autopsy case of acute cor pulmonale and paradoxical systemic embolism due to tumour cell microemboli in a patient with breast cancer. BMJ Case Rep. 2012;2012. Epub 2012/10/05. pmid:23035163; PubMed Central PMCID: PMC4543403.
  23. 23. Veinot JP, Ford SE, Price RG. Subacute cor pulmonale due to tumor embolization. Arch Pathol Lab Med. 1992;116(2):131–4. Epub 1992/02/01. pmid:1733403.
  24. 24. van de Ven PJ, de Jong PC, Jansen GH, Blijham GH. [Microscopic tumor embolisms in metastasized breast carcinoma]. Ned Tijdschr Geneeskd. 1997;141(11):536–40. Epub 1997/03/15. pmid:9190512.
  25. 25. Kawasaki H, Ogura H, Arai Y, Baba S, Kosugi I, Tsutsui Y, et al. Aggressive progression of breast cancer with microscopic pulmonary emboli possessing a stem cell-like phenotype independent of its origin. Pathol Int. 2010;60(3):228–34. Epub 2010/04/21. pmid:20403050.
  26. 26. Moores LK, Burrell LM, Morse RW, Belgrave CH, Balingit AG. Diffuse tumor microembolism: a rare cause of a high-probability perfusion scan. Chest. 1997;111(4):1122–5. Epub 1997/04/01. pmid:9106600.
  27. 27. Soares FA, Pinto AP, Landell GA, de Oliveira JA. Pulmonary tumor embolism to arterial vessels and carcinomatous lymphangitis. A comparative clinicopathological study. Arch Pathol Lab Med. 1993;117(8):827–31. Epub 1993/08/01. pmid:8343048.
  28. 28. Tamura A, Matsubara O. [Pulmonary tumor embolism: relationship between clinical manifestations and pathologic findings]. Nihon Kyobu Shikkan Gakkai Zasshi. 1993;31(10):1269–78. Epub 1993/10/01. pmid:8271660.
  29. 29. Abe H, Hino R, Fukayama M. Platelet-derived growth factor-A and vascular endothelial growth factor-C contribute to the development of pulmonary tumor thrombotic microangiopathy in gastric cancer. Virchows Archiv: an international journal of pathology. 2013;462(5):523–31. Epub 2013/03/29. pmid:23536282.
  30. 30. Yoshii Y, Kawabata Y, Takayanagi N, Araya J, Kuwano K, Sugita Y. Progressive diffuse pulmonary interstitial opacities due to complications of pulmonary tumor emboli: an autopsy case report. Intern Med. 2015;54(8):955–60. Epub 2015/04/17. pmid:25876580.
  31. 31. Goshima H, Tomioka H, Nishio C, Fujii H, Katsuyama E. Reversed halo sign in pulmonary infarction with tumor emboli: a case report. Respir Investig. 2014;52(3):199–202. Epub 2014/05/24. pmid:24853022.
  32. 32. Iwakami S, Sato T, Takagi H, Fujii M, Iwakami N, Yoshimi K, et al. An autopsy case of subacute cor pulmonale due to pulmonary tumor cell emboli in a patient with gastric cancer. Intern Med. 2009;48(12):1057–60. Epub 2009/06/16. pmid:19525598.
  33. 33. Matsuda H, Chida K, Miwa S, Nakano H, Kuwata H, Suzuki K, et al. [An autopsy case of cor pulmonale due to a pulmonary tumor embolism as the first clinical manifestation of occult gastric cancer]. Nihon Kokyuki Gakkai Zasshi. 2002;40(11):910–4. Epub 2003/03/21. pmid:12645114.
  34. 34. Lo Priore E, Fusi-Schmidhauser T. When the pathologist is giving the answer: an unusual case of pulmonary hypertension. Praxis (Bern 1994). 2014;103(18):1081–3. Epub 2014/09/04. pmid:25183617.
  35. 35. Kuraki T, Kobayashi H, Nagata N, Kawai T. [Pulmonary tumor embolism caused by asymptomatic gastric cancer]. Nihon Kyobu Shikkan Gakkai Zasshi. 1997;35(6):641–4. Epub 1997/06/01. pmid:9294298.
  36. 36. Kato H, Shumiya T, Yamauchi M, Miyamoto J, Nakano A, Tsukamoto H, et al. Rapidly progressive symptom development of pulmonary arterial hypertension: a case report of Trousseau syndrome. Heart Vessels. 2014;29(6):873–7. Epub 2013/11/28. pmid:24275907.
  37. 37. Koma Y, Matsuoka H, Ryoke T, Koyama M, Fukumitsu K, Kasai Y, et al. [A case of pulmonary carcinomatous lymphangitis and multiple pulmonary infarctions from gastric cancer]. Nihon Kokyuki Gakkai Zasshi. 2011;49(8):577–82. Epub 2011/09/08. pmid:21894772.
  38. 38. Jakel J, Ramaswamy A, Kohler U, Barth PJ. Massive pulmonary tumor microembolism from a hepatocellular carcinoma. Pathol Res Pract. 2006;202(5):395–9. Epub 2006/02/21. pmid:16488087.
  39. 39. Chan GS, Ng WK, Ng IO, Dickens P. Sudden death from massive pulmonary tumor embolism due to hepatocellular carcinoma. Forensic Sci Int. 2000;108(3):215–21. Epub 2000/03/29. pmid:10737468.
  40. 40. Clark T, Maximin S, Shriki J, Bhargava P. Tumoral pulmonary emboli from angioinvasive hepatocellular carcinoma. Curr Probl Diagn Radiol. 2014;43(4):227–31. Epub 2014/06/21. pmid:24948215.
  41. 41. Papp E, Keszthelyi Z, Kalmar NK, Papp L, Weninger C, Tornoczky T, et al. Pulmonary embolization as primary manifestation of hepatocellular carcinoma with intracardiac penetration: a case report. World J Gastroenterol. 2005;11(15):2357–9. Epub 2005/04/09. pmid:15818754; PubMed Central PMCID: PMC4305827.
  42. 42. Gutierrez-Macias A, Barandiaran KE, Ercoreca FJ, De Zarate MM. Acute cor pulmonale due to microscopic tumour embolism as the first manifestation of hepatocellular carcinoma. Eur J Gastroenterol Hepatol. 2002;14(7):775–7. Epub 2002/08/10. pmid:12169988.
  43. 43. Soares FA, Landell GA, de Oliveira JA. Pulmonary tumour embolism from squamous cell carcinoma of the oesophagus. Eur J Cancer. 1991;27(4):495–8. Epub 1991/01/01. pmid:1827728.
  44. 44. Sentani K, Nakanishi Y, Ojima H, Hamaguchi T, Shimoda T. Esophageal squamous cell carcinoma presenting with systemic arterial embolism. Pathol Int. 2007;57(2):96–100. Epub 2007/02/16. pmid:17300674.
  45. 45. Liang YH, Kuo SW, Lin YL, Chang YL. Disseminated microvascular pulmonary tumor embolism from non-small cell lung cancer leading to pulmonary hypertension followed by sudden cardiac arrest. Lung Cancer. 2011;72(1):132–5. Epub 2011/02/22. pmid:21333371.
  46. 46. Yilmaz S, Galle J, Welker L, Kanzow G. [Right heart failure due to pulmonary tumor microembolism—a rare differential diagnosis]. Pneumologie. 2004;58(6):400–3. Epub 2004/06/25. pmid:15216432.
  47. 47. Nichols L, Saunders R, Knollmann FD. Causes of death of patients with lung cancer. Arch Pathol Lab Med. 2012;136(12):1552–7. Epub 2012/12/01. pmid:23194048.
  48. 48. de Escalante Yanguela B, Rubio Gracia J, Munoz Gonzalez G, Gracia Tello B, Rodero Roldan M, Alastrue Del Castano V. [Microvascular pulmonary tumor embolism in a patient with urothelial tumor]. An Sist Sanit Navar. 2015;38(2):339–43. Epub 2015/10/22. pmid:26486545.
  49. 49. Kitayama H, Yokota T, Kondo T, Sugiyama J, Hirayama M, Oyamada Y, et al. Unusual Development of Pulmonary Tumor Embolism from Controlled Liver Metastases of Transitional Cell Carcinoma: An Autopsy Case. Intern Med. 2016;55(17):2453–6. Epub 2016/09/02. pmid:27580549.
  50. 50. Scheppach W, Krenn V, Eck M, Menzel T, Burrows G, Langenfeld H. [Tumor cell embolism to pulmonary arteries]. Zeitschrift fur Gastroenterologie. 2001;39(8):583–6. Epub 2001/09/15. pmid:11558062.
  51. 51. Kobori G, Yamada H, Hirai S, Higashi Y. [A case of microscopic pulmonary tumor emboli 14 months after total cystectomy]. Hinyokika Kiyo. 2004;50(4):279–81. Epub 2004/06/11. pmid:15188624.
  52. 52. Dhillon SS, Singh DJ, Dass B, Schaub CR. Transitional cell carcinoma manifesting as acute cor pulmonale: cause of microscopic tumor embolism. South Med J. 2001;94(10):1030–2. Epub 2001/11/13. pmid:11702817.
  53. 53. Arisawa C, Fujii Y, Higashi Y, Owada F, Shimizu S, Kaneko K. [Acute respiratory failure resulting from diffuse microscopic pulmonary tumor emboli by bladder cancer: a case diagnosed at autopsy]. Hinyokika Kiyo. 1993;39(5):475–8. Epub 1993/05/01. pmid:8322632.
  54. 54. Suyama N, Mashimoto H, Araki J, Asai S, Ikeno Y, Ikeda T. [An autopsy case of urinary bladder carcinoma with pulmonary infarction and subacute cor pulmonale caused by tumor embolization]. Nihon Kyobu Shikkan Gakkai Zasshi. 1994;32(5):491–6. Epub 1994/05/01. pmid:8084107.
  55. 55. Steiner S, Plehn G, Reinecke P, Cohnen M, Schwartzkopff B, Hennersdorf MG, et al. Disseminated microvascular pulmonary tumor cell embolism: a rare cause of fulminant pulmonary hypertension. Onkologie. 2004;27(6):566–8. Epub 2004/12/14. pmid:15591717.
  56. 56. Bennink R, Van Wijngaerden E, De Roo M, Mortelmans L. Pulmonary tumor microembolism. Nuklearmedizin. 1998;37(4):153–5. Epub 1998/07/03. pmid:9650217.
  57. 57. Masoud SR, Koegelenberg CF, van Wyk AC, Allwood BW. Fatal tumour pulmonary embolism. Respirol Case Rep. 2017;5(1):e00209. Epub 2016/12/30. pmid:28031842; PubMed Central PMCID: PMC5167281.
  58. 58. Kim AE, Haramati LB, Janus D, Borczuk A. Pulmonary tumor embolism presenting as infarcts on computed tomography. J Thorac Imaging. 1999;14(2):135–7. Epub 1999/04/21. pmid:10210489.
  59. 59. Weidemann DM, de Jonge JP, Blessing MH, Doehn MH. [Disseminated tumor cell embolism of the lung as a cause of sudden death during general anesthesia]. Anaesthesist. 1991;40(7):407–9. Epub 1991/07/01. pmid:1928716.
  60. 60. Bergmann I, Weiss M, Schaffner T. [Pulmonary microscopic tumor embolism syndrome]. Dtsch Med Wochenschr. 2006;131(12):618–21. Epub 2006/03/18. pmid:16544237.
  61. 61. van der Burg-de Graauw NC, van Esser JW. [Fatal pulmonary tumour embolism as initial manifestation of an occult coecum tumour]. Ned Tijdschr Geneeskd. 2009;153:A227. Epub 2009/09/30. pmid:19785837.
  62. 62. Okazaki S, Abe T, Takayanagi N, Yasuda M, Sakai F, Kobayashi K, et al. Pulmonary Tumor Embolism Due to Squamous Cell Carcinoma of the Uterine Cervix: A Case Report. In Vivo. 2018;32(2):337–43. Epub 2018/02/25. pmid:29475918; PubMed Central PMCID: PMC5905203.
  63. 63. Vaideeswar P, Aswani Y, Damani S, Singaravel S. Pulmonary microvascular metastases in cervical carcinoma: A case series. J Postgrad Med. 2020;66(3):155–8. Epub 2020/07/18. pmid:32675452; PubMed Central PMCID: PMC7542055.
  64. 64. Nakao Y, Yokoyama M, Yasunaga M, Hara K, Nakahashi H, Iwasaka T. Metastatic tumor extending through the inferior vena cava into the right atrium: a case report of carcinoma of the uterine cervix with para-aortic lymph node metastases. Int J Gynecol Cancer. 2006;16(2):914–6. Epub 2006/05/10. pmid:16681785.
  65. 65. Lovrenski A, Vrekic Z, Skrbic D, Visnjic BA, Vasilijevic M, More LV. An autopsy case of massive pulmonary tumor embolism due to undiagnosed prostatic adenocarcinoma. Forensic Sci Med Pathol. 2020;16(1):152–6. Epub 2019/11/07. pmid:31691070.
  66. 66. Hattori T, Ikegami Y, Matsuyama N, Hamakawa T, Maruyama T, Naiki-Ito A, et al. Microscopic pulmonary tumor embolism from adenocarcinoma of the prostate. IJU Case Rep. 2020;3(5):161–5. Epub 2020/09/12. pmid:32914059; PubMed Central PMCID: PMC7469864.
  67. 67. Nakano M, Miwa K, Kanimoto Y, Ishihara S, Deguchi T. Microscopic pulmonary tumor embolism secondary to adenocarcinoma of the prostate. Hinyokika Kiyo. 2003;49(3):169–72. Epub 2003/05/06. pmid:12728533.
  68. 68. Lambert-Jensen P, Mertz H, Nyvad O, Christensen JH. Subacute cor pulmonale due to microscopic pulmonary tumour cell embolization. J Intern Med. 1994;236(5):597–8. Epub 1994/11/01. pmid:7964440.
  69. 69. Ando H, Ootake Y, Asaka S. Subacute pulmonary hypertension due to pulmonary tumor microembolism as a clinical manifestation of occult gallbladder adenocarcinoma. Jpn Circ J. 1997;61(1):82–6. Epub 1997/01/01. pmid:9070964.
  70. 70. de Luis DA, Darriba J, San Miguel P, Rull SG, Cuesta C, Fogue I. A case of secondary pulmonary hypertension due to microscopic pulmonary tumor cell embolism from gallbladder carcinoma. Respiration. 1997;64(3):244–6. Epub 1997/01/01. pmid:9154680.
  71. 71. Uraguchi K, Kozakura K, Fukuda M, Marunaka H, Doi A, Ohta T, et al. An autopsy case of Trousseau’s syndrome with tumor thrombosis in unknown primary squamous cell carcinoma of the head and neck. Int Cancer Conf J. 2021;10(1):15–9. Epub 2021/01/26. pmid:33489695; PubMed Central PMCID: PMC7797400.
  72. 72. Kitaoka K, Takeda M, Chono Y, Nagashima K. [Multiple cerebral infarction by blood-borne tumor emboli in carcinoma of the mid-pharynx: an autopsy case]. No Shinkei Geka. 1992;20(9):997–1001. Epub 1992/09/01. pmid:1407367.
  73. 73. Nakanishi D, Tanio Y, Tagawa H, Akiyama T, Takashima J, Motone M, et al. [An autopsy of a case of pulmonary hypertension secondary to pulmonary embolization of intrahepatic cholangiocarcinoma]. Gan To Kagaku Ryoho. 2013;40(4):499–502. Epub 2013/07/16. pmid:23848019.
  74. 74. Nabeshima S, Kishihara Y, Nabeshima A, Yamaga S, Kinjo M, Kashiwagi S, et al. Poorly differentiated adenocarcinoma with signet-ring cells of the Vater’s ampulla, without jaundice but with disseminated carcinomatosis. Fukuoka Igaku Zasshi. 2003;94(7):235–40. Epub 2003/09/26. pmid:14509231.
  75. 75. do Nascimento FB, Albieri L, Bento Dos Santos GA, Dolhnikoff M, Bias. Right Cardiac Chambers Involvement by a Malignant Testicular Germ Cell Tumor: An Imaging-pathologic Correlation. Urology. 2016;93:e9–e11. Epub 2016/03/29. pmid:27017904.
  76. 76. Koppl H, Scheer E, Herbst EW. [Extensive pulmonary tumor embolisms of anaplastic thyroid gland carcinoma as a rare cause of hemorrhagic pleural effusion in an 88-year-old patient]. Pneumologie. 1993;47(10):593–6. Epub 1993/10/01. pmid:8259368.
  77. 77. Srettabunjong S, Chuangsuwanich T. Inferior Vena Cava Tumor Thrombosis Secondary to Metastatic Uterine Cancer: A Rare Cause of Sudden Unexpected Death. J Forensic Sci. 2016;61(2):555–8. Epub 2016/07/13. pmid:27404631.
  78. 78. Fujiwara R, Narita M, Kageyama S, Kawauchi A, Nakayama T, Nishi N, et al. [A Case of Synchronous Multiple Metastases in which the Origin Could Not Be Identified by Routine Examination]. Hinyokika Kiyo. 2016;62(9):473–7. Epub 2016/10/21. pmid:27760972.
  79. 79. Mangiapan G, Parrot A, Antoine M, Mayaud C. [Pulmonary artery hypertension due to tumor micro-embolism]. Rev Mal Respir. 1995;12(1):62–5. Epub 1995/01/01. pmid:7899672.
  80. 80. Sperling BL, Cockcroft DW, Chibbar R. Microscopic pulmonary tumour embolism: an unusual presentation of thymic carcinoma. Can Respir J. 2002;9(5):347–50. Epub 2002/11/01. pmid:12410327.
  81. 81. Chai L, Ong KC, Ng SB. A case of pulmonary tumour embolism mimicking miliary tuberculosis. Respirology. 2000;5(3):297–9. Epub 2000/10/07. pmid:11022995.
  82. 82. Grass H, Schuff A, Staak M, Dienes HR, von Both I. Tumor embolism as a cause of an unexpected death: a case report. Pathol Res Pract. 2003;199(5):349–52. Epub 2003/08/12. pmid:12908527.
  83. 83. Schmid S, Ohlschlegel C, Nagel W, Zeisel C, Muller J, Rothermundt C. Pulmonary embolism in a patient with primary renal synovial sarcoma: the important differential diagnosis of tumor embolism and its therapeutic implications. Case Rep Oncol. 2013;6(2):331–8. Epub 2013/07/31. pmid:23898277; PubMed Central PMCID: PMC3724140.
  84. 84. Oyama Y, Nishida H, Kondo Y, Kusaba T, Kadowaki H, Harada T, et al. Pulmonary tumor thrombotic microangiopathy associated with extramammary Paget’s disease: An autopsy case report. Pathol Int. 2020;70(9):680–5. Epub 2020/07/09. pmid:32638479.
  85. 85. Skalidis EI, Parthenakis FI, Zacharis EA, Datseris GE, Vardas PE. Pulmonary tumor embolism from primary cardiac B-cell lymphoma. Chest. 1999;116(5):1489–90. Epub 1999/11/13. pmid:10559123.
  86. 86. Hoshino A, Matsuo A, Suzuki K, Nishibori Y, Inoue K, Tanaka T, et al. [Sudden death due to pulmonary tumor embolism from testicular tumor: a case report]. J Cardiol. 2006;48(4):227–32. Epub 2006/10/28. pmid:17066627.
  87. 87. Saitoh J, Sakurai H, Suzuki Y, Katoh H, Takahashi T, Nakano T. Metastatic angiosarcoma of the lung with alveolar hemorrhage. Jpn J Radiol. 2009;27(9):381–4. Epub 2009/11/28. pmid:19943151.
  88. 88. Schweyer S, Meyer-Venter R, Lorf T, Sattler B, Fayyazi A. [Malignant fibrous histiocytoma of the liver]. Zeitschrift fur Gastroenterologie. 2000;38(3):243–8. Epub 2000/04/18. pmid:10768247.
  89. 89. Katz ES, Rosenzweig BP, Rorman D, Kronzon I. Diagnosis of tumor embolus to the pulmonary artery by transesophageal echocardiography. J Am Soc Echocardiogr. 1992;5(4):439–43. Epub 1992/07/01. pmid:1510861.