Pulmonary tumour thrombotic microangiopathy

A 44-year-old female patient with known malignancy (stage IV cervical cancer, phase 1 clinical trial with bad prognosis) presented with slowly progressive shortness of breath. She had been recently diagnosed with proximal DVT and an IVC filter had been placed along with anticoagulant therapy.

The patient’s symptoms worsened so a pulmonary CTA was performed.

There was no evidence of pulmonary embolism in main, principal, lobar or segmental pulmonary arteries.

Signs of pulmonary hypertension:
- Enlarged pulmonary trunk.
- Increased main pulmonary artery (pulmonary trunk) to ascending aorta ratio.
- Straightening of the interventricular septum.
- Dilatation of the right cardiac cavities.

Lung parenchyma findings:

- No pulmonary infarcts were seen.
- Subtle ground-glass opacification with a peribronchovascular distribution.
- Bilateral ill-defined centrilobular micronodules (some in a tree-in-bud pattern).
- Smooth thickening of fissures and interlobular septa.

Pulmonary embolism (PE) is a common cause of acute cardiovascular disorder with variable haemodynamic impact; going from silent PE to a high mortality presentation, despite advances in the diagnostic techniques and treatment available nowadays.[1]

There are many known entities that can cause PE, although it usually develops as secondary to lower limb deep vein thrombosis. Depending on the extent and duration of the occlusion, the patient’s basal situation and the presence of vasospasm, a degree of pulmonary hypertension may develop. [2]

PE remains one of the top indications for performing a CT angiogram in the emergency department, usually being a straightforward diagnosis by demonstrating a filling defect in one or more pulmonary arteries. However, the diagnosis can be challenging in some cases, where clear signs of pulmonary hypertension exist and no arterial filling defect is identified. In such cases, and especially in oncologic patients, we need to keep in mind the possibility of pulmonary tumour thrombotic microangiopathy (PTTM).

PTTM describes tumour cell microemboli with occlusive fibrointimal remodelling in small vessels and lymphatics leading to precapillary pulmonary hypertension. [3]. Clinically patients present with an acute/subacute onset of severe progressive dyspnoea secondary to cor pulmonale. Diagnostic techniques include: CT-angio, HRCT, cardiac catheterisation, PET-CT and ultimately definitive diagnosis by pathology.

Price LC et al. also describe that up to a quarter of autopsy specimens from patients dying of carcinoma show evidence of PTTM, which means it is most likely an underdiagnosed entity. Most cases are published in Japanese series and are mainly related to gastric adenocarcinomas. [3]

Radiographic features are best depicted on HRCT with findings similar to our case: ill-defined centrilobular micronodules, diffuse smooth interlobular septal thickening, and patchy peribronchovascular ground glass opacities along with signs of pulmonary hypertension and right heart chambers overload. [4]

In our case CT pulmonary angiography showed no filling defects and due the clinical context and the rest of the findings, PTTM was suspected. Pulmonary SPECT perfusion findings were consistent with perfusion defects, backing up the suspicion of PTTM. The patient passed away two days after being admitted in our center.

Written informed patient consent for publication has been obtained.