A CASE OF PULMONARY TUMOR THROMBOTIC MICROANGIOPATHY (PTTM) FROM INCIDENTAL FINDING OF POORLY DIFFERENTIATED ESOPHAGEAL ADENOCARCINOMA

Case Presentation: 71M with PMHx of pAfib on Eliquis, HTN, and CKD3a admitted to MICU as transfer for AHRF with severe pulmonary HTN s/p intubation, pressor support, NGT placement during planned TEE cardioversion for persistent Afib. On arrival active upper GIB was present through his NGT and emergent EGD revealed large distal esophageal mass; cytology indicated poorly differentiated adenocarcinoma. Other notable work-up include: WBC 10.5H, hgb 11.5L, platelet 127,000L, haptoglobin < 30L, fibrinogen 504, D-dimer 695H, LDH 309H, Tbili 2.0H, peripheral smear with schistocytes, anisopoikilocytosis, polychromasia, negative rheumatic work-up, Cr 2.16 (baseline ~1.7), BNP 328H, normal troponin. CT chest with enlarged main pulmonary artery, extensive bilateral tree-in-bud opacities with multiple areas of focal ground-glass opacities, and LAD throughout mediastinum, hila, R supraclavicular region. NM lung V/Q scan with low probability of PE but obstructive findings at lung bases. EKG Afib w/ HR 79. TTE with normal LVEF >55%, severely elevated pulmonary artery and RV pressures, and severely enlarged RV, RA, and IVC.In absence of PE and rheumatic disease, his presentation was attributed to PTTM given findings on TTE, imaging, blood-work. Given his overall poor prognosis, he transitioned to hospice.

Discussion: PTTM is a very rare complication of metastatic cancer that is difficult to identify clinically and is predominantly diagnosed postmortem. Evidence of diffuse centrilobular “tree-in-bud” disease that was much more pronounced than seen on prior CTA was highly suggestive of PTTM, especially with negative infectious work-up. Furthermore, in the setting of poorly differentiated esophageal adenocarcinoma, this presentation may represent tumor emboli. Our patients V/Q scan also suggests a mild “moth eaten” appearance that would support the idea that obliterative pulmonary angiopathy exists. The data on effective treatment for pulmonary tumor emboli is insufficient but it is generally directed at the primary tumor. Different proposed therapies, such as combination of chemotherapy with dexamethasone, warfarin, and aspirin, and pulmonary vasodilators, do not improve the prognosis under such circumstances, but may improve patient symptoms. The medical literature also mentions that the appearance of PH secondary to PTTM may be mediated either by VEGF or PDGF. This suggests that ramucirumab, a VEGFR2 inhibitor, may be beneficial in the treatment of PTTM, just like imatinib, a TKI that acts against PDGF. However, given the abysmal cancer prognosis and worsening respiratory status, Palliative Medicine was consulted for our patient, and he elected for hospice care. Given the rising prevalence of PTTM in patients with adenocarcinomas, it may be necessary to emphasize the existence of this complication in Medicine and subspecialty training programs, and that it should be taken for consideration in patients who begin to show alterations in lung function and cannot be explained by other causes.

Conclusions: Most cases of PTTM are associated with adenocarcinoma.3 The pathophysiology stems from activated coagulation cascade, dysregulated complement system, oxidative stress in B12 deficiency by tumor cells. Consequently, therapeutic focus is on long-term anticoagulation prophylaxis, and endothelial and platelet-derived growth factor inhibitors.4 There is also a need for classification systems since PTTM is vastly under-diagnosed, either postmortem or from elevated suspicion during final stages of malignancy.