Annals of Thoracic Medicine Official publication of the Saudi Thoracic Society, affiliated to King Saud University
Search Ahead of print Current Issue Archives Instructions Subscribe e-Alerts Login 
Home Email this article link Print this article Bookmark this page Decrease font size Default font size Increase font size

Table of Contents   
Year : 2012  |  Volume : 7  |  Issue : 3  |  Page : 168-169
Pulmonary tumor thrombotic microangiopathy caused by gastric cancer

1 Department of Pathology, Osaka Medical College, Osaka, Japan
2 Department of Respiratory Medicine, Osaka Medical College, Osaka, Japan
3 Department of Radiology, Osaka Medical College, Osaka, Japan

Date of Submission08-Aug-2011
Date of Acceptance07-Oct-2011
Date of Web Publication21-Jul-2012

Correspondence Address:
Hiroko Kuwabara
Department of Pathology, Osaka Medical College, 2-7 Takatsuki, Osaka 569-8686
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1817-1737.98853

Rights and Permissions


Pulmonary tumor thrombotic microangiopathy (PTTM) is a fatal cancer-related pulmonary complication with rapidly progressing dyspnea, and occasionally induces sudden death. Here, we describe a postmortem-diagnosed PTTM case caused by gastric cancer, with the complaint of progressing dyspnea for 5 days.He did not have any abdominal symptoms or cancer history. PTTM should be considered in patients with rapidly worsening respiratory conditions, even if there is no cancer history.

Keywords: Dyspnea, gastric cancer, PTTM

How to cite this article:
Kuwabara H, Yoshida S, Takasu T, Yuki M, Goto I, Hanafusa T, Shibayama Y. Pulmonary tumor thrombotic microangiopathy caused by gastric cancer. Ann Thorac Med 2012;7:168-9

How to cite this URL:
Kuwabara H, Yoshida S, Takasu T, Yuki M, Goto I, Hanafusa T, Shibayama Y. Pulmonary tumor thrombotic microangiopathy caused by gastric cancer. Ann Thorac Med [serial online] 2012 [cited 2023 Apr 1];7:168-9. Available from:

Pulmonary tumor thrombotic microangiopathy (PTTM), which was first reported by Von Herbay et al., [1] causes narrowing of the pulmonary artery and induces a respiratory disturbance with pulmonary hypertension, right-side heart failure, and sudden death. The most frequent cause of PTTM is gastric cancer. [1] PTTM is histologically characterized by widespread tumor emboli together with fibrocellular intimal proliferation and thrombus formation in small pulmonary arteries and arterioles in patients with metastatic carcinomas. The clinical course is very rapid, and antemortem diagnosis is usually difficult, particularly in patients without a cancer history. [2] PTTM induces occasional sudden death following rapidly developing dyspnea, and awareness of PTTM is important for respiratory physicians.

   Case Report Top

A 43-year-old Japanese man visited a neighboring hospital complaining of dyspnea on effort, dry cough, and rhinorrhea for 2 weeks. He did not show any abdominal symptoms and had no cancer history. A chest computed tomography scan revealed diffuse centrolobular tiny nodules and thickening of both bronchovascular bundles and interlobular septa in lungs, and bronchiolitis and lymphangiosis carcinomatosa were suspected [Figure 1]. He was admitted to our hospital for further examination and treatment. Laboratory tests showed the following findings: white blood cells, 13 990/μl; platelets, 229 x 10 3 /μl; plasma D-dimer, 7.0 μg/ml (normal <2.0); carcinoembryonic antigen, 4.0 ng/ml (<5.0); CA19-9, 95.7 U/ml (<37); and vascular endothelial growth factor (VEGF), 832 pg/ ml (<120). His oxygen saturation was 90% when breathing room air. Antibiotic administration and oxygen supplementation therapy were performed, and a whole-body screening was planned. However, his respiratory condition deteriorated and, on the fifth day after admission, he suddenly complained of severe dyspnea and died.
Figure 1: Chest computed tomography scan showing diffuse tiny nodules and the swelling of bronchovascular bundles

Click here to view

A postmortem examination revealed an ulcerated tumor, measuring 12.5 × 9 cm, in the stomach angle. Histologically, the tumor was a poorly differentiated adenocarcinoma with remarkable lymphatic permeation that had invaded into the serosa. Multiple abdominal lymph nodes were involved. Ascites was 200 ml and peritoneal dissemination was absent. The left and right lungs weighed 620 and 740 g, respectively. Hemorrhagic infarctions were present in the right lower lobe, and macroscopic thrombi were absent in the pulmonary arteries. Microscopic examination revealed widespread fibrin thrombi and fibrocellular and fibromuscular intimal proliferation with or without gastric cancer cells, resulting in luminal stenosis and occlusion in the small pulmonary arteries [Figure 2]a,b. These findings were compatible with PTTM. Lymphangiosis carcinomatosa and mediastinal lymph node involvement were also seen. Carcinoma cells in the stomach and lungs were immunohistochemically positive for VEGF [Figure 2]c. The heart weighed 385 g and showed dilatation of the right ventricle. The liver weighed 1 645 g and showed congestion, probably owing to congestive heart failure. Every organ except for the stomach lacked a space-occupying tumor mass.
Figure 2: (a) Obstruction of a pulmonary artery (H and E, x40), (b) High-power view of an artery (H and E, x400), (c) Immunopositivity for vascular endothelial growth factor among the tumor cells (x200)

Click here to view

   Discussion Top

The pathogenesis of PTTM is generally explained as follows. Tumor cells metastasize to the pulmonary vascular system, activate the coagulation cascade, and release inflammatory mediators and growth factors, resulting in deposition of platelets and fibrin, fibrocellular subintimal proliferation, and smooth muscle colonization. [3] The components of the tissue factor-VEGF system, especially VEGF, are proposed to be the mediators that induce PTTM. [2] In fact, our case had carcinoma cells that were positively stained for VEGF and elevated serum VEGF. Clinically, PTTM-related manifestations are rapid, and an antemortem diagnosis is usually difficult, as seen in our case. Previously, a gastric cancer patient with an antemortem diagnosis of PTTM by serum VEGF and D-dimer elevation, probably owing to the activated coagulation cascade, and specimens from a transbronchial lung biopsy and video-assisted thoracoscopic surgery, was cured by corticosteroid, anticoagulants, and oral anticancer drug therapies. [4] For early antemortem diagnosis of PTTM, serum VEGF and D-dimer measurements may be effective for screening. In addition, PTTM is frequently associated with lymphangiosis carcinomatosa, [1] and the latter may be a predisposing factor to PTTM.

In summary, it is important to suspect PTTM as a differential diagnosis for rapidly worsening respiratory conditions, not only in patients with cancer, but also in patients without a cancer history. The early diagnosis may cure the PTTM patients.

   References Top

1.Von Herbay A, Illes A, Waldherr R, Otto HF. Pulmonary tumor thrombotic microangiopathy with pulmonary hypertension. Cancer 1990;66:587-92.   Back to cited text no. 1
2.Chinen K, Tokuda Y, Fujiwara M, Fujioka Y. Pulmonary tumor thrombotic microangiopathy in patients with gastric carcinoma: An analysis of 6 autopsy cases and review of the literature. Pathol Res Pract 2010;206:682-9.   Back to cited text no. 2
3.Pinckard JK, Wick MR. Tumor-related thrombotic pulmonary microangiopathy: Review of pathologic findings and pathophysiologic mechanisms. Ann Diagn Pathol 2000;4:154-7.  Back to cited text no. 3
4.Miyano S, Izumi S, Takeda Y, Tokuhara M, Mochizuki M, Matsubara O, et al. Pulmonary tumor thrombotic microangiopathy. J Clin Oncol 2007;25:597-9.  Back to cited text no. 4


  [Figure 1], [Figure 2]

This article has been cited by
1 Clinical Course of Suspected Diagnosis of Pulmonary Tumor Thrombotic Microangiopathy: A 10-Year Experience of Rapid Progressive Right Ventricular Failure Syndrome in Advanced Cancer Patients
Minjung Bak, Minyeong Kim, Boram Lee, Eun Kyoung Kim, Taek Kyu Park, Jeong Hoon Yang, Duk-Kyung Kim, Sung-A Chang
Korean Circulation Journal. 2023; 53
[Pubmed] | [DOI]
2 Pulmonary Tumor Embolism and Pulmonary Tumor Thrombotic Microangiopathy Causing Rapidly Progressive Respiratory Failure: A Case Series
Kartikeya Rajdev, Ujjwal Madan, Sean McMillan, Kyle Wilson, Kurt Fisher, Ashley Hein, Amol Patil, Sabin Bista, Daniel Hershberger, Brian Boer
Journal of Investigative Medicine High Impact Case Reports. 2022; 10: 2324709622
[Pubmed] | [DOI]
3 A Rare Case of Pulmonary Tumor Thrombotic Microangiopathy Associated with Micropapillary Urothelial Carcinoma of the Urinary Bladder: An Autopsy Case
Takafumi Kitazono, Kazuya Tsubouchi, Ritsu Ibusuki, Katsuhiro Inoue, Kimitaka Miyajima, Junichi Motoshita, Yuki Okamatsu, Taishi Harada
Internal Medicine. 2021; 60(17): 2843
[Pubmed] | [DOI]
4 Pulmonary tumor thrombotic microangiopathy: a systematic review
Rohit H. Godbole, Rajan Saggar, Nader Kamangar
Pulmonary Circulation. 2019; 9(2): 1
[Pubmed] | [DOI]
5 The diagnostic challenge of pulmonary tumour thrombotic microangiopathy as a presentation for metastatic gastric cancer: a case report and review of the literature
Andrew LK. Ho,Patryk Szulakowsi,Waria HS. Mohamid
BMC Cancer. 2015; 15(1)
[Pubmed] | [DOI]
6 Occult Gastric Cancer Presenting as Hypoxia from Pulmonary Tumor Thrombotic Microangiopathy
Rohan Mandaliya,Salman Farhat,Dipesh Uprety,Mamtha Balla,Apurva Gandhi,Richard Goldhahn,Herbert Auerbach,Chris Christensen,Conrad Reed,Sidney Cohen
Journal of Gastric Cancer. 2014; 14(2): 142
[Pubmed] | [DOI]
7 A case report of pulmonary tumor thrombotic microangiopathy (PTTM) caused by esophageal squamous cell carcinoma
Takeshi Fujishiro,Kiyohiko Shuto,Toru Shiratori,Tuguaki Kono,Yasunori Akutsu,Masaya Uesato,Isamu Hoshino,Kentaro Murakami,Shunsuke Imanishi,Toru Tochigi,Yoko Yonemori,Hisahiro Matsubara
Esophagus. 2013;
[Pubmed] | [DOI]
8 A Case of Pulmonary Tumor Thrombotic Microangiopathy Diagnosed by Transbronchial Lung Biopsy and Treated with Chemotherapy and Long-Term Oxygen and Anticoagulation Therapies
Atsushi Kitamura,Naoki Nishimura,Torahiko Jinta,Rika Suda,Yasuhiko Yamano,Genta Ishikawa,Yutaka Tomishima,Tsuyoshi Hamaoka,Koyu Suzuki,Naohiko Chohnabayashi
Case Reports in Pulmonology. 2013; 2013: 1
[Pubmed] | [DOI]


Print this article  Email this article
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Article in PDF (1,908 KB)
    Citation Manager
    Access Statistics
    Reader Comments
    Email Alert *
    Add to My List *
* Registration required (free)  

   Case Report
    Article Figures

 Article Access Statistics
    PDF Downloaded717    
    Comments [Add]    
    Cited by others 8    

Recommend this journal