Pulmonary Tumor Thrombotic Microangiopathy Associated With Gastric Cancer: Clinical Characteristics and Outcomes

Abstract

Purpose: Pulmonary tumor thrombotic microangiopathy (PTTM) is a fatal complication of gastric cancer (GC). This study aimed to evaluate the clinical characteristics, outcomes, and immunohistochemical profiles of patients with GC-induced PTTM.

Materials and methods: From 2011 to 2023, 8 patients were clinically diagnosed with PTTM associated with GC antemortem. Clinical features and outcomes were reviewed, and immunohistochemical staining for c-erbB-2, MutL protein homolog 1, and programmed cell death ligand-1 was performed.

Results: The median patient age was 56 years (range, 34-66 years). In all the patients, the tumors exhibited either ulceroinfiltrative or diffusely infiltrative gross morphology. The median tumor size was 5.8 cm (range, 2.0 cm-15.0 cm). Poorly differentiated adenocarcinoma was the most common histological type (6/8, 75%), followed by signet ring cell carcinoma (1/8, 12.5%) and moderately differentiated adenocarcinoma (1/8, 12.5%). Chest computed tomography revealed ground-glass opacities (7/8, 87.5%) or tree-in-bud signs (2/8, 25.0%) without definite evidence of pulmonary thromboembolism. Disseminated intravascular coagulation was present in 62.5% (5/8) of the patients diagnosed with PTTM. C-erbB-2 was positive in one patient (1/8, 12.5%). One patient who received palliative chemotherapy after developing PTTM survived for 35 days, whereas the other 7 patients who did not receive chemotherapy after developing PTTM survived for 7 days or less after PTTM diagnosis.

Conclusions: Most patients with GC-induced PTTM had an undifferentiated-type histology, infiltrative morphology, and extremely poor survival. Palliative chemotherapy may benefit patients with GC-induced PTTM; however, further studies are needed to explore the potential of targeted therapy in these patients.

Keywords: Gastric cancer; Prognosis; Pulmonary tumor thrombotic microangiopathy.

Fig. 1. Representative imaging findings of a patient with Bormann type IV advanced gastric cancer and pulmonary tumor thrombotic microangiopathy (#8 in Table 1). On endoscopy (A), gastric folds were diffusely thickened and showed easy touch bleeding. The stomach could not be fully inflated despite air injection. Chest computed tomography (B) showed multifocal ill-defined ground-glass opacities. Echocardiography (C) showed dilated RV cavity size (base: 44.1 mm and mid: 38.2 mm at apical 4 chamber view) and increased RV systolic pressure (TR Vmax = 84.0 mmHg).

RV = right ventricular; LV = left ventricular; RA = right atrial; LA = left atrial.

Fig. 2. Pathologic findings of primary gastric cancer and lung biopsy showing tumor thrombotic microangiopathy (patient #2 in Table 1). In the hematoxylin and eosin staining (×10) of the surgically resected stomach specimen (A), poorly differentiated tumor cells with unrecognizable tubular structures were observed. In the hematoxylin and eosin staining (×10) of the surgically resected lung specimen (B), embolic tumor clusters with morphologic characteristics similar to those in the stomach were occluding the arterioles showing concentric fibrocelullar intimal proliferation.