Familial polyposis

(Chest 1994; 106:275-77)

A 49-year-old man was admitted with 3 weeks of progressively severe dyspnea. The patient had familial polyposis coli for which he underwent total colectomy with ileorectal anastomosis 15 years previously. Two years before admission, he presented with iron deficiency anemia due to adenocarcinoma confined to the rectum and had an abdominal perineal resection.

Physical Examination

Vital signs: temperature, 37[degrees]C; pulse, 108/min; respirations, 36/min; and BP, 138/92 mm Hg. General: severe respiratory distress with cyanosis. Chest: normal breath sounds. Cardiac: prominent [P.sub.2]. No jugular venous distention. Abdomen: functioning ileostomy. No hepatomegaly or HJ reflux. Extremities: cyanotic nail beds. No peripheral edema. Neurologic: normal.

Laboratory Findings

Hemoglobin, 18.7 g/dl; WBC, 16,800/[mm.sup.3] without left shift; electrolytes, liver enzymes, BUN, creatinine, normal. ABG (room air): pH, 7.51; [Pco.sub.2], 23 mm Hg; [Po.sub.2], 39 mm Hg. Chest radiograph: normal. ECG: normal axis, no acute changes. Doppler venous study of both lower extremities: normal. Echocardiogram: dilated right ventricle with hypokinesis, dilated right atrium with tricuspid regurgitation, estimated pulmonary artery systolic pressure, 60 mm Hg. Ventilation-perfusion lung scan: indeterminate for pulmonary thromboembolism (Fig 1). Pulmonary angiogram: "pruning" of vasculature bilaterally without evidence of intraluminal filling defect, measured pulmonary artery pressure, 77/40 mm Hg.

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Hospital Course

Severe refractory hypoxemia persisted, and the patient died 48 h after admission after developing intractable hypotension.

What is the probable diagnosis?

Answer: Multiple microscopic tumor emboli to the lungs with hypoxic respiratory failure and cor pulmonale.

Pulmonary tumor emboli occur when aggregates of tumor cells enter the pulmonary vasculature. Although the pathway for entrance into the pulmonary vasculature is uncertain, emboli are thought to arise from hepatic vein invasion from liver metastases, venous invasion at the site of the primary tumor, or transit of malignant cells into the venous circulation through the thoracic duct. Once in the pulmonary vascular bed, tumor emboli may lodge in large pulmonary arteries or in the smaller branches of the pulmonary arterial tree if they are microscopic in size. Histologic sections demonstrate clusters of tumor cells in association with platelet-fibrin thrombi that may initiate obliterative arteritis. Because most tumor emboli either degenerate or lie dormant within the pulmonary circulation, they are not considered true metastases.

Tumor embolization as a mode of spread of cancer to the lungs is uncommon. Tumor emboli were found in only 26 of 1,085 (2.4 percent) autopsies of solid malignant neoplasms; there were no cases of tumor emboli to major pulmonary vessels. In a selected autopsy series of 366 patients who died with breast cancer, gastric carcinoma, hypernephroma, hepatoma, and choriocarcinoma, tumor emboli were found in 26 percent; most tumor emboli from all reported tumors were microscopic. Large tumor emboli, although uncommon, resulted only from hepatoma and choriocarcinoma.

Although tumor emboli may be the initial manifestation of an underlying malignancy, they more commonly occur in the setting of previously established malignant disease. Of 26 cases of tumor emboli found at autopsy in one series, only 4 did not have malignancy suspected prior to death.

A wide variety of neoplasms give rise to tumor emboli. In one series of 164 patients, hepatoma was the most frequent (29 percent), followed by carcinoma of the breast (18 percent), kidney (18 percent), and stomach (9 percent). Carcinoma of the prostate, choriocarcinoma, and multiple other primary sites were reported less frequently.

The diagnosis of multiple tumor emboli often is not considered as the clinical presentation and laboratory data are nonspecific. Dyspnea is the most common symptom, but cough, pleuritic chest pain, and hemoptysis also occur. Autopsy series have also reported that tumor emboli may be silent and discovered as incidental findings in 50 to 70 percent of cases. When the lungs are involved by widespread emboli, as in the present patient, respiratory failure, pulmonary hypertension, and cor pulmonale can result. Acute pulmonary thromboemboli should always be considered in the differential diagnosis of unexplained respiratory failure, especially in a patient with known malignancy.

Imaging modalities can suggest the diagnosis in patients who present with acute or subacute dyspnea, hypoxemia, and normal lung fields on chest radiograph. In cases of microscopic tumor emboli, a ventilation-perfusion lung scan typically shows multiple, bilateral, mismatched subsegmental perfusion defects. Pulmonary angiography fails to show intraluminal filling defects, thus excluding acute thromboemboli. However, if large tumor emboli are present, the pulmonary angiogram will show filling defects in large vessels similar to those seen in thromboemboli.

Confirmation of microscopic tumor emboli requires histologic examination of lung tissue. Sampling of microvascular cytology in blood obtained from a "wedged" pulmonary artery catheter or at the time of pulmonary angiography can be a valuable alternative to lung biopsy especially in the critically ill, unstable patient.

The impact of tumor emboli on survival is variable. Emboli may be found as incidental findings at autopsy or may contribute to or be a primary cause of death. The prognosis of patients with tumor emboli can vary with the site of the primary tumor. Emboli arising from hepatoma and breast cancer are more likely to be a primary cause of death comared to stomach cancer; hypernephroma tumor emboli appear to rarely be a primary cause of death. Thus, microscopic tumor emboli are not universally fatal, and some patients can stabilize or improve allowing for treatment of the underlying malignancy.

As tumor emboli can be difficult to diagnose, heightened physician awareness is necessary. The importance of an accurate diagnosis rests largely on the need to avoid inappropriate therapy, such as anticoagulation for presumed pulmonary thromboembolic disease. As newer chemotherapeutic agents are developed, the diagnosis of tumor emboli may become more important if more effective treatment can be directed against the underlying malignancy.

Autopsy in the present patient showed microscopic tumor emboli involving the liver, adrenal glands, and pancreas, with widespread tumor deposits throughout the pulmonary vasculature. Multiple retroperitoneal and intra-abdominal lymph nodes contained metastatic adenocarcinoma.

CLINICAL PEARLS

1. Microscopic multiple tumor emboli to the lungs can lead to hypoxemia, pulmonary hypertension, acute or subacute cor pulmonale, and death in patients with cancer. A high index of suspicion is necessary as the clinical presentation may resemble that of pulmonary thromboemboli.

2. In most patients with tumor emboli, ventilation-perfusion lung scanning will show multiple, mismatched, subsegmental perfusion defects, but the pulmonary angiogram shows no intraluminal filling defects.

3. When right-sided heart catheterization or pulmonary angiography is performed in the course of diagnostic evaluation, pulmonary hypertension is noted, and cytologic examination of blood withdrawn from a pulmonary artery catheter may demonstrate neoplastic cells and confirm the clinical diagnosis of tumor emboli.

4. The diagnosis of tumor emboli may become more important clinically, if more effective treatment becomes available to treat the underlying malignancy.

SUGGESTED READING

Case Records of the Massachusetts General Hospital (Case 43-1980). N Engl J Med 1980; 303:1049-56

Case Records of the Massachusetts General Hospital (Case 25-1991). N Engl J Med 1991; 324:1795-1804

Chan CK, Hutcheon MA, Hyland RH, Smith GJW, Patterson BJ, Matthay RA. Pulmonary tumor embolism: a critical review of clinical imaging, and hemodynamic features. J Thorac Imag 1987; 2:4-14

Kane RD, Hawkins HK, Miller JA, Noce PS. Microscopic tumor emboli associated with dyspnea. Cancer 1975; 36:1473-82

Lukl P. Pulmonary microvascular cytology in the dyspneic cancer patient. Arch Pathol Lab Med 1992; 116:129-30

Schriner RW, Ryu JH, Edwards WD. Microscopic pulmonary tumor embolism causing subacute cor pulmonale: a difficult antemortem diagnosis. Mayo Clin Proc 1991; 66:143-48

Veinot JP, Ford SE, Price RG. Subacute cor pulmonale due to tumor embolization. Arch Pathol Lab Med 1992; 116:131-34

Winterbauer RH, Elfenbein IB, Ball WC Jr. Incidence and clinical significance of tumor embolization to the lungs. Am J Med 1968; 45:271-90

(*)From the Section of Pulmonary Disease, Medical Center of Delaware, Wilmington; and the Jefferson Medical College, Thomas Jefferson University, Philadelphia.

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