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Pulmonary tumor embolism and lymphangitic carcinomatosis in adults: Epidemiology, etiology, and pathogenesis

Pulmonary tumor embolism and lymphangitic carcinomatosis in adults: Epidemiology, etiology, and pathogenesis
Literature review current through: Jan 2024.
This topic last updated: Dec 04, 2023.

INTRODUCTION — The lungs are a prominent target for the embolization of any material larger than approximately 10 microns that gains access to the venous or lymphatic circulation. This includes venous thrombi, air, amniotic fluid, fat, injected foreign material, and tumor. The malignant pulmonary embolization syndromes, pulmonary tumor emboli and lymphangitic carcinomatosis, are associated with a poor prognosis. Thus, prompt recognition is critical so that therapy can be initiated in a timely fashion.

The epidemiology, etiology, and pathogenesis of pulmonary tumor emboli and pulmonary lymphangitic carcinomatosis are reviewed here. The clinical features, diagnostic evaluation, and management of pulmonary tumor emboli and pulmonary lymphangitic carcinomatosis and the embolization of venous thrombi, air, amniotic fluid, fat, or foreign material are discussed separately. (See "Epidemiology and pathogenesis of acute pulmonary embolism in adults" and "Air embolism" and "Amniotic fluid embolism" and "Fat embolism syndrome" and "Foreign body granulomatosis" and "Pulmonary tumor embolism and lymphangitic carcinomatosis in adults: Diagnostic evaluation and management".)

TERMINOLOGY — Pulmonary tumor embolism and lymphangitic carcinomatosis are considered end-stage manifestations of malignancy. The terminology for both disorders is often used interchangeably and while they are often considered as morphologically distinct from each other, overlap is not infrequent [1]. Both disorders need to be distinguished from pulmonary metastases, which are identified pathologically as solid isolated lesions that have the classic morphologic features of lung invasion. (See "Overview of the initial evaluation, diagnosis, and staging of patients with suspected lung cancer".)

Pulmonary tumor embolism — Pulmonary tumor embolism refers to the identification of tumor within pulmonary blood vessels on pathologic lung samples. Invasion of the surrounding interstitium is not typically seen, a feature that distinguishes it from pulmonary metastases. However, tumor may sometimes also be concomitantly seen within lymphatic vessels. Due to the prominent involvement of pulmonary vasculature, patients with this syndrome are more likely to present with the signs and symptoms of pulmonary hypertension and acute right heart failure. (See "Pulmonary tumor embolism and lymphangitic carcinomatosis in adults: Diagnostic evaluation and management", section on 'Clinical presentation'.)

Pulmonary lymphangitic carcinomatosis — Lymphangitic carcinomatosis is morphologically defined by the presence of tumor within pulmonary lymphatics. Tumor cells within pulmonary veins are not typically seen; however, tumor cells can invade the interstitium resulting in thickened bronchovascular bundles and interstitial septae. Since pulmonary capillary obstruction is not a feature of this disorder, patients with this syndrome are less likely to present with the signs and symptoms of pulmonary hypertension and acute right heart failure. (See "Pulmonary tumor embolism and lymphangitic carcinomatosis in adults: Diagnostic evaluation and management", section on 'Clinical presentation'.)

EPIDEMIOLOGY — The true incidence of pulmonary tumor embolism and lymphangitic carcinomatosis is unknown since the diagnosis is most often post mortem. In our experience, as clinical syndromes they are rare presentations among patients with malignancy and rare causes of hypoxemic respiratory failure. Due to the subtle presentation and diagnostic delay, the incidence is probably higher on autopsy than on biopsy specimens. One autopsy series of 65,181 cancer patients identified tumor embolism in 0.19 percent and tumor invasion into a large vein in 0.11 percent [2]. Comparatively, thrombotic pulmonary embolism was identified in 2.3 percent of patients. In a 2021 series of autopsies from patients with solid tumors, the incidence of pulmonary tumor embolism was 3 percent [3].

ETIOLOGY — Common malignancies that are associated with these disorders are similar and are listed in the table (table 1). However, any malignant tumor has the potential to result in pulmonary tumor emboli or lymphangitic carcinomatosis with case reports of cases due to cutaneous angiosarcoma and lip cancer [1,4-11].

The risk of tumor emboli appears to be the greatest with renal cell and hepatocellular carcinoma as well as mucin-secreting adenocarcinomas of the breast, lung, stomach, kidney, and colon. Tumor emboli can also complicate prostate cancer, pancreatic cancer, and choriocarcinoma, and is a rare presentation of other malignancies including chondrosarcoma and lymphoma. Common malignancies associated with pulmonary lymphangitic carcinomatosis are similar, particularly adenocarcinoma of the stomach, lung, head and neck, and esophagus. Since many of these malignancies involve thoracic lymph nodes, this has led to the theory that tumors such as these cause lymphangitis via retrograde flow to the lungs. (See 'Pathogenesis' below.)

PATHOGENESIS — The pathogenesis of pulmonary tumor embolism and lymphangitic carcinomatosis is poorly understood. It is not studied and most theories are based upon the histologic appearance of autopsy specimens as well as indirect data derived from studies that investigate the mechanisms of traditional invasive metastatic disease. It is thought that, similar to solid pulmonary metastases, tumor gains access to the lungs to induce local pathology [1,12,13]. However, the resultant morphologic change that ensues is different for all three entities. While tumor embolism predominantly involves pulmonary vasculature, lymphangitic carcinomatosis primarily involves the lymphatic system, and solid metastases invade all components of pulmonary parenchymal tissue.

Accessing the lungs — Tumor cells likely gain access to the lung via venous and lymphatic circulations or possibly via transdiaphragmatic passage (eg, peritoneal carcinomatosis) [1,12,13].

Access to blood and lymphatic vessels may be due to direct invasion of nearby vessels (eg, pulmonary vein, inferior vena cava, thoracic lymphatics). In one autopsy series of cancer patients, tumor invasion into a large vein was identified in 0.11 percent of autopsies, 13 percent of whom had concomitant tumor emboli [2]. Alternatively, tumor fragments may be released into the tumor's neovasculature or neolymphatics.

Most of the circulating tumor cells are destroyed by circulatory mechanical forces, shear forces, or the host's immune system [14,15]. However, some tumor cells, for ill-defined reasons, reach the lungs to induce pathology.

It is unclear whether diaphragmatic translocation of tumor cells from the peritoneum is a viable mechanism but it has been proposed in older case reports of malignancies involving the peritoneum [16-18].

Inducing lung pathology — It has been proposed that tumor emboli and lymphangitic carcinomatosis are spectrums of the same disease since components of both disorders can be found pathologically in some cases. However, this is not universal and the two disorders frequently exist as separate entities on pathologic specimens [1,14]. Thus, the mechanism that underlies the induction of tumor pathology in the lung may be different for each entity.

Pulmonary tumor embolism – Tumor cells appear to become trapped within the pulmonary circulation and trigger the coagulation cascade to obstruct the pulmonary vessels. Reactive concentric medial hypertrophy and intimal fibrosis of the pulmonary vessels ("obliterative arteritis") may also contribute to the obliterative pathology [19,20]. The process can progress to complete and irreversible obstruction of pulmonary vessels; this is in contrast to obstruction by venous thromboemboli, which is generally reversible via the process of recanalization. This process is sometimes referred to as pulmonary tumor thrombotic microangiopathy.

When the pulmonary vasculature becomes obstructed, ventilation-perfusion matching becomes impaired and pulmonary vascular resistance increases, which may impair gas exchange and cause pulmonary hypertension and cor pulmonale, which are prominent clinical features of this condition [4].

Intraluminal tumor emboli do not appear to proliferate intravascularly or invade the vessel wall to spread locally; thus, they should not be considered metastases. Lung metastasis requires malignant cells to adhere to lung-specific adhesion molecules on the endothelium, produce enzymes that degrade the basement membrane and lung extracellular matrix, and grow in association with lung-specific growth factors [14,21].

Lymphangitic carcinomatosis – It is presumed that tumor cells trapped within lymphatics result in local obstruction and fluid accumulation. Bronchovascular bundle and alveolar septal thickening may be due to local edema, and the presence of nodules in some cases may suggest that tumor cells in lymphangitic carcinomatosis can grow locally [22]. Invasion of surrounding tissue is not typically observed. Pulmonary vessels tend not to be involved, explaining why pulmonary hypertension is a less common presentation among this population.

SUMMARY AND RECOMMENDATIONS

Terminology - The terminology for Pulmonary tumor emboli and lymphangitic carcinomatosis is often used interchangeably. However, pulmonary tumor embolism refers to the identification of tumor within pulmonary blood vessels on pathologic lung samples whereas pulmonary lymphangitic carcinomatosis refers to the identification of tumor in pulmonary lymphatic vessels. (See 'Terminology' above.)

Epidemiology - The true incidence of pulmonary tumor embolism and lymphangitic carcinomatosis is unknown but clinical experience and autopsy studies suggest that both conditions affect less than 1 percent of patients with cancer. (See 'Epidemiology' above.)

Etiologies - Malignancies that are associated with pulmonary tumor emboli or lymphangitic carcinomatosis are similar (table 1). Any malignant tumor has the potential to result in both disorders. However, the risk appears to be the greatest in patients with renal cell and hepatocellular carcinoma as well as adenocarcinoma of the breast, stomach, colon, and lung. (See 'Etiology' above.)

Pathogenesis - The pathogenesis of these disorders is poorly understood. Pulmonary tumor emboli likely spread to the lungs via the venous circulation and become trapped within pulmonary vessels to cause vascular thrombosis and obstruction; they do not proliferate or spread locally. In lymphangitic carcinomatosis, tumor cells likely gain access to the lung via lymphatic vessels, resulting in local obstruction and fluid accumulation. (See 'Pathogenesis' above.)

  1. 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; 117:827.
  2. Sakuma M, Fukui S, Nakamura M, et al. Cancer and pulmonary embolism: thrombotic embolism, tumor embolism, and tumor invasion into a large vein. Circ J 2006; 70:744.
  3. He X, Anthony DC, Catoni Z, Cao W. Pulmonary tumor embolism: A retrospective study over a 30-year period. PLoS One 2021; 16:e0255917.
  4. Roberts KE, Hamele-Bena D, Saqi A, et al. Pulmonary tumor embolism: a review of the literature. Am J Med 2003; 115:228.
  5. King MB, Harmon KR. Unusual forms of pulmonary embolism. Clin Chest Med 1994; 15:561.
  6. Chan CK, Hutcheon MA, Hyland RH, et al. Pulmonary tumor embolism: a critical review of clinical, imaging, and hemodynamic features. J Thorac Imaging 1987; 2:4.
  7. Peixoto LS, Valiante PM, Rodrigues RS, et al. An unusual cause of tree-in-bud pattern: pulmonary intravascular tumor embolism caused by chondrosarcoma. Lung 2015; 193:151.
  8. Hibino M, Akazawa K, Hikino K, Oe M. Pulmonary tumor embolism secondary to uterine corpus carcinosarcoma mimicking pulmonary thromboembolism. Intern Med 2012; 51:2603.
  9. Pérez Baztarrica G, Nieva N, Gariglio L, et al. Images in cardiovascular medicine. Primary cardiac lymphoma: a rare case of pulmonary tumor embolism. Circulation 2010; 121:2249.
  10. Liau CT, Jung SM, Lim KE, Shih HN. Pulmonary lymphangitic sarcomatosis from cutaneous angiosarcoma: an unusual presentation of diffuse interstitial lung disease. Jpn J Clin Oncol 2000; 30:37.
  11. Babu S, B S, M G, Salih S. A rare presentation of pulmonary lymphangitic carcinomatosis in cancer of lip: case report. World J Surg Oncol 2011; 9:77.
  12. Park JH, Seo HS, Park SK, et al. Spontaneous systemic tumor embolism caused by tumor invasion of pulmonary vein in a patient with advanced lung cancer. J Cardiovasc Ultrasound 2010; 18:148.
  13. Lindqvist C, Lepäntalo M, Jungell P. Lymphangitis carcinomatosa of the lungs. An unusual complication of oral cancer. Br J Oral Maxillofac Surg 1988; 26:228.
  14. Bassiri AG, Haghighi B, Doyle RL, et al. Pulmonary tumor embolism. Am J Respir Crit Care Med 1997; 155:2089.
  15. Lianidou ES, Strati A, Markou A. Circulating tumor cells as promising novel biomarkers in solid cancers. Crit Rev Clin Lab Sci 2014; 51:160.
  16. CHANDLER GN, TELLING M. Lymphangitis carcinomatosa. Br Med J 1952; 2:639.
  17. Hendin AS, Deveney CW. Postmortem demonstration of abnormal deep pulmonary lymphatic pathways in lymphangitic carcinomatosis. Cancer 1974; 33:1558.
  18. Soares FA, Landell GA, de Oliveira JA. Pulmonary tumour embolism from squamous cell carcinoma of the oesophagus. Eur J Cancer 1991; 27:495.
  19. Goldhaber SZ, Dricker E, Buring JE, et al. Clinical suspicion of autopsy-proven thrombotic and tumor pulmonary embolism in cancer patients. Am Heart J 1987; 114:1432.
  20. Shields, DJ, Edwards, WD. Pulmonary hypertension attributable to neoplastic emboli: An autopsy study of 20 cases and a review of the literature. Cardiovasc Pathol 1992; 1:279.
  21. Schmitt M, Harbeck N, Thomssen C, et al. Clinical impact of the plasminogen activation system in tumor invasion and metastasis: prognostic relevance and target for therapy. Thromb Haemost 1997; 78:285.
  22. Bruce DM, Heys SD, Eremin O. Lymphangitis carcinomatosa: a literature review. J R Coll Surg Edinb 1996; 41:7.
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