**36. History and epidemiology**

In 1897, Schmidt (M. B. Schmidt, 1903) first described pulmonary tumor embolization in a patient with gastric carcinoma. Autopsy showed the pulmonary bed was massively occluded by tumor emboli and pathology was similar to gastric tumor cells. It was not until 1937 that Brill and Robertson (Brill & Robertson, 1937) described the clinical syndrome of sub acute cor-pulmonale due to multiple tumor emboli to the pulmonary microvasculature. This syndrome is rare and exceedingly difficult to recognize before death. Since then pulmonary tumor embolism has been described in a variety of malignancies.

The estimated incidence of pulmonary tumor embolism is 3-26% among patients with solid tumors as reported by autopsy series (Bast et al., 2000; Kane et al., 1975; Shields & Edwards, 1992). Despite the relative prevalence at autopsy, the diagnosis is infrequently made ante mortem and thus the incidence of clinically significant tumor embolism is unclear (C. K. Chan et al., 1987). Retrospective chart reviews demonstrate that only 8% of patients with pathological evidence of tumor emboli have documented morbidity and mortality (Kane et al., 1975; Shields & Edwards, 1992).

#### **37. Etiology**

94 Pulmonary Embolism

be transferred to intensive care unit. AFE still carries significant morbidity which includes neurological deficit in significant proportions of mothers as well as newborn. Neonatal

survival is reported to be at 70%.

 • Acute fetal compromise • Cardiac arrhythmias or arrest

• Maternal haemorrhage

cardiorespiratory compromise

finding fetal squames or hair in the lungs

• Shortness of breath

**35. Tumor embolism** 

Types:

"days"

malignancies.

to months

**36. History and epidemiology** 

 • Coagulopathy • Convulsion • Hypotension

*Either* In the absence of any other clear cause

Acute maternal collapse with one or more of the following features:

• Premonitory symptoms, e.g. restlessness, numbness, agitation, tingling

*Or* Women in whom the diagnosis was made at post-mortem examination by

occluded by aggregates of tumor cells accompanied by platelet-fibrin thrombosis.

Table 10. UK Obstetric Surveillance System (UKOSS) criteria for defining cases of AFE

Pulmonary tumor emboli are defined as clumps of malignant cells within the lumina of pulmonary arteries and arterioles (Kane et al., 1975). Microscopic pulmonary tumor emboli involve the small pulmonary arteries, arterioles and alveolar septal capillaries which are

1. "Acute" tumor emboli - "massive" tumor emboli that can result in symptoms over

2. "Sub-acute" tumor emboli - multiple small emboli resulting in "symptoms" over weeks

In 1897, Schmidt (M. B. Schmidt, 1903) first described pulmonary tumor embolization in a patient with gastric carcinoma. Autopsy showed the pulmonary bed was massively occluded by tumor emboli and pathology was similar to gastric tumor cells. It was not until 1937 that Brill and Robertson (Brill & Robertson, 1937) described the clinical syndrome of sub acute cor-pulmonale due to multiple tumor emboli to the pulmonary microvasculature. This syndrome is rare and exceedingly difficult to recognize before death. Since then pulmonary tumor embolism has been described in a variety of

The estimated incidence of pulmonary tumor embolism is 3-26% among patients with solid tumors as reported by autopsy series (Bast et al., 2000; Kane et al., 1975; Shields & Edwards,

Excluding women with maternal haemorrhage as the first presenting feature in whom there was no evidence of early coagulopathy or

The risk appears to be greatest with mucin secreting adenocarcinomas of the breast, lung, stomach and colon. However, PTE has also been reported in hepatocellular, prostate, renal cell and choriocarcinomas. Other rare associations are listed below (K. E. Roberts et al., 2003).

Table 11. Primary Tumors associated with Tumor Embolism

#### **38. Pathology**

Histological studies of tumor emboli in humans and animals have provided some insights into the fate of pulmonary tumor emboli. Schimdt noted that tumor emboli are usually associated with intravascular platelet-fibrin rich thrombi. As a result, cancer cells become fewer and degenerative in appearance during the organization of these thrombi. The tumor emboli have no tendency to invade the arterial wall (Winterbauer et al., 1968). Necropsy studies and animal model studies suggest that tumor emboli are destroyed or remain latent and are not truly metastases. Soares et al (Soares et al., 1993) studied 222 consecutive autopsies of cancer cases and detected pulmonary hypertensive arteriopathy

Non-Thrombotic Pulmonary Embolism 97

Pulmonary Cement Embolism (PCE) is a complication of Percutaneous Vertebroplasy (PVP) and Balloon Kyphoplasty which are minimally invasive procedures used to treat osteoporotic and other vertebral fractures (Galibert et al., 1987; Garfin et al., 2001;Gigante & Pierangeli, 2008; McDonald et al., 2008; Oner et al., 2006; Stoffel et al., 2007; Wu & Fourney, 2005). Polymethylmethacrylate (PMMA, "cement" ) leakage is a frequent occurrence during these procedures and the source of PCE (Gangi et al., 1999; Garfin et al., 2001; Hauck et al., 2005; Hodler et al., 2003; R. Schmidt et al., 2005; Vasconcelos et al., 2002; Yeom et al., 2003). The risk of pulmonary cement embolism (PCE) ranges from 3.5% to 23% for osteoporotic fractures (Anselmetti et al., 2005; Choe et al., 2004; Duran et al., 2007; Y. J. Kim et al., 2009). A recent report suggested a prevalence of 8.8% (Gill et al., 2010). Exact incidence is difficult to estimate as many are asymptomatic and escape detection. Patients with malignant lesions of the vertebrae might be at a higher risk of developing PCE due to damaged cortical substance and increased vascularity, while technical factors such as inappropriate viscosity of the cement at the time of injection, lack of visual guidance and higher cement volume injected during the procedure increase the risk of PCE (Baroud et al., 2006; Bohner et al., 2003; Choe et al., 2004; Deramond et al., 1998).The clinical spectrum following PMMA leakage is broad: asymptomatic extravasation into surrounding tissues, features of nerve root compression (Kelekis et al., 2003; Laredo & Hamze, 2005; Ratliff et al., 2001), asymptomatic and symptomatic pulmonary cement embolism (Anselmetti et al., 2005; Choe et al., 2004; Duran et al., 2007; Y. J. Kim et al., 2009), even cardiac perforation (S. Y. Kim et al., 2005; Lim et al., 2008; Schoenes et al., 2008; Son et al., 2008) and death (H. L. Chen et al., 2002; Monticelli et al., 2005; Stricker et al., 2004; Yoo et al., 2004) have been reported. Fat embolism occurring simultaneously with cement embolism may also contribute to the clinical picture (Aebli et al., 2002; Rauschmann et al., 2004). Clinically PCE cannot be distinguished from thrombotic pulmonary embolism (Bernhard et al., 2003; Jang et al., 2002; Padovani et al., 1999; Tozzi et al., 2002). Diagnosis is based on history and imaging which shows presence of radio-opaque densities (Figs 6 a&b). There is not enough evidence to underlay treatment guidelines. Since cement is regarded as "thrombogenic", (Francois et al., 2003; Perrin et al., 1999; Righini et al., 2006; Tozzi et al., 2002) anticoagulation for 6 months is recommended for symptomatic patients or patients with central PCE. Asymptomatic patients with peripheral PCE should have close clinical follow up with no anticoagulation. Surgical embolectomy may be considered for exceptional cases of central embolism. Routine chest roentogenogram should be obtained after PVP and BKP regardless of the symptoms as many patients are

Gas embolism (GE) is mainly ambient "air" embolism (AE) but also includes other gases such as carbon dioxide, nitrous oxide, nitrogen and helium. It is a rare and potentially fatal condition. There are 2 main types of GE, i.e, venous and arterial. They are distinguished by the mechanism of entry. Venous GE (VGE) occurs usually as a complication of iatrogenic procedures such as vascular catheter placement, mechanical ventilation and rarely surgical procedures (pulmonary lung biopsy, open heart surgeries, craniotomy). Arterial GE causes ischemia. As little as 0.5ml of air can result in coronary ischemia, cardiac arrhythmias,

**40. Pulmonary cement embolism** 

asymptomatic.

**41. Gas embolism** 

serious brain damage and even death.

with proliferative endarteritis. Thus, PTE may be pathologically indistinguishable from other forms of pulmonary arterial hypertension, except for the notable absence of plexiform lesions. Some investigators describe tumor emboli as possessing an unusual level of resistance to recannulation (as compared to thromboembolism) and therefore likely lead to progressive and irreversible obstruction of the pulmonary vascular bed (Winterbauer et al., 1968).

**Pathophysiology:** Pulmonary vasculature provides the first capillary bed to the circulating tumor cells. The process of pulmonary metastasis consists of sequential steps that includes intravascular and/or lymphatic invasion of the lung by the neoplastic cells. Large scale autopsy studies suggest that tumor cells spread to the pulmonary vasculature in basically 4 ways (Kane et al., 1975; Winterbauer et al., 1968):


**Clinical features:** In most patients, primary malignancy was established when tumor emboli were noted. The signs and symptoms are non-specific. Patients with large proximal emboli have rapid onset of symptoms due to acute right heart failure indistinguishable from the presentation of a massive thromboembolism. Lymphangitic carcinomatosis and microvascular disease involving small pulmonary arteries, follow a more deliberate and progressive course resulting in subacute cor pulmonale.

**Physical examination** shows evidence of pulmonary hypertension and signs of right heart dysfunction. Common findings included: tachypnea, tachycardia, cyanosis, hypotension, elevated Jugular venous distension (JVD), audible pulmonic sound (P2), ascites and peripheral edema. Although considered "classic", signs of right heart failure are only reported in 15% to 20% of patients with this syndrome (Veinot et al., 1992).

**Diagnosis:** Ante-mortem diagnosis of pulmonary tumor embolism can be very difficult due to lack of distinctive features compared to thrombo-embolism which is more common. Diagnosis often made via tissue specimens from open lung biopsy or autopsy. Pulmonary arterial sampling (in a wedge position) has resulted in diagnosis in a few cases (Masson & Ruggieri, 1985; K. E. Roberts et al., 2003).
