Disseminated intravascular coagulation complicating diagnosis of ROS1‐mutant non‐small cell lung cancer: A case report and literature review

Abstract

Disseminated intravascular coagulation (DIC) is a rare paraneoplastic complication in advanced solid malignancies, with success of treatment and survival dependent on treatment of the underlying malignancy. Best estimates suggest an incidence of 1.6-6.8% in cancer, with risk factors being advanced disease, older age, and adenocarcinoma, especially of lung origin. Few cases, however, have reported on an association between DIC and oncogene-addicted lung cancers, especially those containing ROS proto-oncogene 1 (ROS1) mutations, however precedent exists to suggest increased prothrombotic rates in tumors harboring this mutation. We present a young woman with ROS1-mutant non-small-cell lung cancer who presented in DIC and subsequently developed complications of both hemorrhage and thrombosis. Following initiation of targeted treatment, rapid resolution of laboratory coagulation derangement was observed and clinical improvement quickly followed. This event underscores the need for rapid evaluation of lung molecular panels and the dramatic resolution of lifethreatening illness that can occur with institution of appropriate therapy. This case contributes to growing evidence for a possible underlying link between oncogene addicted tumors and abnormalities of coagulation.

Thrombosis in Lung Cancer Research Trends: A Bibliometric Analysis

“…In recent years, a large number of studies have found that ROS1 is also inextricably linked to the occurrence of thrombotic events in lung cancer. Woodford et al found an association between ROS1 and thrombotic events in lung cancer in a case review of patients with ROS1-mutated non-small cell lung cancer [21] . In a prospective phase II study, Chiari et al found that the incidence of venous thrombosis in patients with ROS1rearranged non-small cell lung cancer was three to ve times higher than in patients with normal nonsmall cell lung cancer [22] .…”

Progress of non-small-cell lung cancer with ROS1 rearrangement

“…The main pathological types are adhesive, vesicular, or solid glandular cancers; a few are squamous-cell, multicellular, or large-cell cancer (Park et al, 2019), more than 90% of which express thyroid transcription factor-1 (TTF-1), mostly diagnosed as phase III-IV, high incidence of brain transfusions (Drilon et al, 2021). Compared to other types of NSCLC, ROS1-positive NSCLC has a significantly increased risk of developing thromboembolic diseases (Shah et al, 2021;Woodford et al, 2021;Zhu et al, 2021), but the underlying mechanism remains unclear.…”

ROS-1 Fusions in Non-Small-Cell Lung Cancer: Evidence to Date

“…Miliary forms of lung metastases have also been described [ 29 ]. Several authors reported a heightened thromboembolic risk of ROS-1-rearranged tumors compared with NSCLCs harboring non-rearranged ROS-1 [ 30 ], and even rarer cases of thrombotic microangiopathies [ 31 ] and disseminated intravascular coagulation [ 32 ]. Although the underlying mechanisms remain to be elucidated, interaction between extracellular carcinoid mucins secreted into the bloodstream and platelet (P-) and leukocyte (L-) selectins could trigger platelet activation and the formation of microthrombi responsible for thromboembolic events [ 33 ].…”