Kartikeya Rajdev, MBBS
Fellow, Pulmonary, Critical Care & Sleep Medicine
University of Nebraska Medical Center, Omaha
Omaha, Nebraska, United States
Disclosure information not submitted.
Sean McMillan, MD
Resident, Internal Medicine
University of Nebraska Medical Center, Omaha, United States
Disclosure information not submitted.
Ujjwal Madan, MBBS
Medical Student
University College of Medical Sciences, New Delhi, United States
Disclosure information not submitted.
Kyle Wilson, MD
Resident, Internal Medicine
University of Nebraska Medical Center, Omaha, United States
Disclosure information not submitted.
Ashley Hein, MD
Resident, Anatomic and Clinical Pathology
University of Nebraska Medical Center, Omaha, United States
Disclosure information not submitted.
Kurt Fisher, MD, PhD
Assistant Professor, Anatomic and Clinical Pathology
University of Nebraska Medical Center, Omaha, United States
Disclosure information not submitted.
Amol Patil, MD
Associate Professor, Pulmonary, Critical Care & Sleep Medicine
University of Nebraska Medical Center, Omaha, United States
Disclosure information not submitted.
Brian Boer, MD, PhD
Assistant Professor, Pulmonary, Critical Care & Sleep Medicine
University of Nebraska Medical Center, Omaha, United States
Disclosure information not submitted.
Title: Pulmonary Tumor Thrombotic Microangiopathy causing Respiratory Failure: Undiagnosed until Autopsy
Introduction: Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare etiology for rapidly progressive dyspnea in the setting of malignancy and is often fatal. It is most frequently associated with gastrointestinal adenocarcinoma. Antemortem diagnosis of PTTM remains a clinical challenge due to its rapidly progressive nature.
Description: A 41 Y/O female, non-smoker with no PMH p/w cough and shortness of breath for a few weeks. She required oxygen supplementation by nasal cannula. Work-up for infectious etiology was negative. Her chest X-ray showed diffuse interstitial prominence. CT scan showed mild centrilobular nodules disease, interlobular septal thickening and prominent central pulmonary arteries. Numerous small sclerotic lesions in the spine, pelvis, and sternum were detected. Mural thickening of the stomach was also noted. The patient underwent a pelvic bone biopsy. An echocardiogram showed dilated right atrium and ventricle with PASP of 90mmHg. Right heart catheterization confirmed severe pre-capillary pulmonary hypertension and reduced cardiac output. She developed worsening hypoxemic respiratory failure and was started on diuretics, ionodilators, and inhaled epoprostenol. The patient had a cardiac arrest and died within four days of presentation. An autopsy showed extensive lymphovascular tumor thrombosis with tumor cell aggregates in pulmonary vessels and lymphatics. Fibrocellular intimal and smooth muscle proliferation was confirmed with special staining. Pelvic bone biopsy suggested poorly-differentiated adenocarcinoma likely arising from the upper gastrointestinal tract.
Discussion: PTTM represents an advanced form of pulmonary tumor microembolism (PTE). While in PTE, tumor cell nests occlude the small pulmonary arteries, in PTTM, these cell nests mediate the deposition of platelets and fibrin, induce inflammation, cytokine, and growth factor release and activation of coagulation factors. This leads to fibrointimal proliferation, raises pulmonary vascular resistance, and leads to acute right heart failure and death. Although there is no definitive therapy for PTE/ PTTM, treatment options to target PTTM include tumor burden reduction with chemotherapy, ionotropes, pulmonary vasodilators, endothelin receptor antagonists, steroids, warfarin, aspirin, PDGF, and VEGF inhibitors.