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Newly Diagnosed Profound Hypoxia and Pulmonary Hypertension
Author: Jami Silflow, MD, Eric H-M Yang, MD, Guy diSibio, MD, Samuel French, MD, Anton Mlikotic, MD, and William W. Stringer, MD
Last Revised: Wed, 10-Sep-2008
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Newly Diagnosed Profound Hypoxia and Pulmonary Hypertension

Jami Silflow, MD, Eric H-M Yang, MD, Guy diSibio, MD, Samuel French, MD, Anton Mlikotic, MD, and William W. Stringer, MD

Case Report

A 43-year-old African American female, who had been diagnosed with a subdural hematoma 2 weeks earlier at an outside hospital, presented to the emergency department with worsening headaches and slurred speech. Aside from the neurologic findings, the physical examination was normal. A computed tomography (CT) scan of her head showed an acute on chronic subdural hematoma. The patient was also noted to be extremely hypoxic (Pulse Oximeter 98%99% on 15 liters of oxygen via a non-rebreather mask) and tachypneic (respiratory rate 26 breaths/minute) upon presentation. The neurosurgical team rapidly evacuated the hematoma; however, postoperatively, they were unable to wean the patient off the ventilator due to marked hypoxia on high FIO2 levels. Arterial blood gas tests showed a pH of 7.44, pCO2 of 35, pO2 of 59 on 60% FIO2; the chest radiograph was unremarkable. Due to concern for a pulmonary embolism, a spiral CT examination was performed.

Radiologic Findings

The chest CT scan showed no evidence of pulmonary embolism, but did show bilateral patchy areas of ground glass opacification, interlobar septal thickening in the lung fields, a right lateral breast mass with axillary lymphadenopathy, and bilateral breast implants (Figure 1).

Due to the profound hypoxia out of proportion to the parenchymal lung disease, and the right ventricular chamber dilation noted on the CT scan, an echocar-

Figure 1. Chest CT scan


Proceedings of UCLA Healthcare - VOLUME 12 (2008) Proceedings of UCLA Healthcare - VOLUME 12 (2008) Proceedings of UCLA Healthcare - VOLUME 12 (2008)

diogram was performed. The echocardiogram showed a severely dilated right ventricle with markedly reduced systolic function, a large right atrium, 4+ tricuspid regurgitation, and severe pulmonary hypertension with a right ventricular systolic pressure of 88 mmHg. A bubble study was also performed and it was markedly positive for a right to left intracardiac shunt (Figure 2).

A right heart catheter was placed which verified the markedly elevated pulmonary artery pressures. There was no response to infused epoprostenol, the patient's hypoxemia worsened despite aggressive ventilatory support, and the patient expired. An autopsy was performed.

Pathologic Findings

The autopsy showed extensive metastatic breast cancer with metastases to the thoracic cavity, lymph nodes, liver, bone, kidneys, pituitary, dura, and brain (Figure 3). The autopsy documented that tumor embolization to the lungs (small pulmonary arteries) resulted in severe pulmonary hypertension (Figure 3B). The patient also had arterial embolization of her breast cancer via a patent foramen ovale to systemic sites, including the kidney (Figure 3C).

Final Autopsy Diagnosis

Final autopsy diagnosis was metastatic breast carcinoma with severe hypoxia and pulmonary hypertension with right to left shunt via a patent foramen ovale resulting in arterial embolization of tumor cells.

Clinical Discussion

This patient presented with a severe hypoxia and rapidly expired. The CT scan showed a breast mass; however, the diagnosis of metastatic breast cancer was unexpected and only definitively made at autopsy. The major features of her clinical presentation were severe pulmonary hypertension and hypoxia refractory to supplemental oxygen suggestive of a right to left shunt.

Tumor embolization to the lungs has been grouped into 4 categories: 1) microscopic pulmonary tumor emboli occluding small arteries and arterioles; 2) emboli which occlude large, proximal pulmonary arteries; 3) microvascular invasion through lymphatic

spread; and 4) a combination of these findings.1 We describe a patient with microscopic pulmonary tumor embolism, causing pulmonary hypertension. Patients with microscopic pulmonary tumor embolism may present with subacute cor pulmonale, with onset of symptoms over the course of a few weeks. The initial laboratory evaluation of a patient typically shows hypoxemia with a clear chest xray, right ventricular systolic pressures exceeding 50 mmHg, and an abnormal ventilation-perfusion scan.2

Radiological Discussion

The diagnostic utility of radiographs can be limited since chest x-rays are frequently normal. Computed tomography scans can show multiple subsegmental peripheral perfusion defects, and this has been called a "segmental contour."2 Dilated and "beaded" peripheral pulmonary arteries have been described with intravascular tumor emboli3; however, pulmonary angiograms in several previous case reports were negative for evidence of large vessel emboli.1,2,4,5 Ventilation perfusion scans may reveal a segmental contour or "mottled" appearance with a normal ventilation scan.2 Transthoracic echocardiograms typically show elevation of right ventricular systolic pressures exceeding 50 to 60 mm Hg. Multiple malignancies have been linked to this phenomenon including breast, liver, pancreatic, gastric, and bladder cancers, however breast represents the majority of these cases.

Pathologic Discussion

Although tumor microembolism to the lung is not uncommon in metastatic breast cancer, it is rarely recognized as a presenting feature of breast cancer. In one necropsy study, microscopic tumor emboli were found in 2% to 26% of patients with solid malignant lesions, and these were thought to contribute to the patient's death in up to 8% of these cases.2 The diagnosis, which requires a tissue biopsy for confirmation, is difficult even if the suspicion for metastatic breast cancer is high. Although pulmonary tumor embolism causing pulmonary hypertension is a known phenomenon,6 it is frequently only discovered postmortem. The reason for this is related to its infrequent occurrence relative to the other more common causes of hypoxemia. Microscopic pulmonary tumor embolism is characterized by the occlusion of small pulmonary arteries, arterioles, and alveolar septal capillaries by aggregates of tumor cells. The most common initial clinical symptoms include subacute progressive dyspnea that can vary in time length, from a few weeks to months. Confirmation of the diagnosis of microscopic tumor embolism usually requires open-lung or transbronchial lung biopsy.1,4,5,7 More recent papers have reported an innovative and less invasive procedure, namely microvascular cytology obtained from a pulmonary artery catheter.6,8,9 In this technique, the catheter is placed in a wedge position and blood is aspirated from the pulmonary arterial port. Despite some false positives with this method, it is useful to consider in a patient presenting with severe pulmonary hypertension where tumor emboli is being considered and other more invasive procedures are not practical.

Konduri et al7 has reported a complete clinical response to chemotherapy in one case of pulmonary artery tumor embolization secondary to breast adenocarcinoma. The patient received letrozole, an aromatase inhibitor. It appears that symptomatic tumor microembolism is more responsive to treatment than lymphangitic carcinomatosis in the lung.

With regards to the presence of dural metastasis causing subarachnoid hemorrhage in this patient, a recent review by Kunii et al10 identified approximately 51 cases of spontaneous subdural hematomas from dural metastasis. The most common tumors involved with dural metastasis are stomach, prostate, and breast, with adenocarcinoma being the most common histological type. Other complicating factors predisposing the patient to subdural bleeding with malignancy included the development of disseminated intravascular coagulation caused by the malignancy or thrombocytopenia from bone marrow infiltration by tumor. The prognosis in these patients overall was poor.


In patients with a known or suspected malignancy (especially breast) presenting with dyspnea and evidence of pulmonary hypertension, tumor microembolism should be considered as a possible etiology. We report an unusual case of microscopic pulmonary tumor embolism from an undiagnosed breast cancer leading to severe pulmonary hypertension. The patient rapidly deteriorated and died. The report also details the rare phenomena of widespread dissemination of tumor related to paradoxical microembolization via a patent foramen ovale, and a subdural hematoma from dural metastasis of breast cancer.


  1. Kane RD, Hawkins HK, Miller JA, Noce PS. Microscopic pulmonary tumor emboli associated with dyspnea. Cancer. 1975 Oct;36(4):1473-82.

  2. Schriner RW, Ryu JH, Edwards WD. Microscopic pulmonary tumor embolism causing subacute cor pulmonale: a difficult antemortem diagnosis. Mayo Clin Proc. 1991 Feb;66(2):143-8. Erratum in: Mayo Clin Proc. 1991 Apr;66(4):439.

  3. Shepard JA, Moore EH, Templeton PA, McLoud TC. Pulmonary intravascular tumor emboli: dilated and beaded peripheral pulmonary arteries at CT. Radiology. 1993 Jun;187(3):797-801.

  4. Feller HA, Janis JF. Pulmonary hypertension, resulting from tumor emboli to pulmonary arteries. Dis Chest. 1968 Jul;54(1):68-70.

  5. Gajdos C, Nierman DM, Moqtaderi FF, Brower ST, Lento P, Bleiweiss IJ. Microscopic Pulmonary Tumor Emboli: An Unusual Presentation of Breast Cancer. Breast J. 2000 Jul;6(4):273-275.

  6. Bhuvaneswaran JS, Venkitachalam CG, Sandhyamani S. Pulmonary wedge aspiration cytology in the diagnosis of recurrent tumour embolism causing pulmonary arterial hypertension. Int J Cardiol. 1993 Jun;39(3):209-12. Review.

  7. Konduri S, Khan Q, Stites S. Pulmonary hypertension caused by metastatic breast cancer and its response to antihormone therapy and chemotherapy. Breast J. 2007 Sep-Oct;13(5):506-8.

  8. Masson RG, Krikorian J, Lukl P, Evans GL, McGrath J. Pulmonary microvascular cytology in the diagnosis of lymphangitic carcinomatosis. N Engl J Med. 1989 Jul 13;321(2):71-6.

  9. Masson RG, Ruggieri J. Pulmonary microvascular cytology. A new diagnostic application of the pulmonary artery catheter. Chest. 1985 Dec;88(6):908-14.

  10. Kunii N, Morita A, Yoshikawa G, Kirino T. Subdural hematoma associated with dural metastasis. A case report. Neurol Med Chir (Tokyo). 2005 Oct;45(10):519-22.

Submitted on April 14, 2008

Newly Diagnosed Profound Hypoxia and Pulmonary Hypertension
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