Prenatal imaging and immunohistochemical analysis of congenital peribronchial myofibroblastic tumor

Abstract

A 32-year-old pregnant woman, gravida 4 para 1, was referred to us at 27 weeks' gestation because of fetal hydrops. Ultrasound examination revealed a male fetus with a large homogeneous mass occupying the whole mediastinum with encasement of the great vessels and bronchus (Figure 1 and Videoclip S1). The tumor had a spiculated margin and infiltrated deep into adjacent tissues, suggestive of a sarcoma or other malignancy (Videoclip S2). Subsequent karyotyping following amniocentesis provided a normal result. Maternal blood tests were negative for active infection of adenovirus, toxoplasma and cytomegalovirus. Fetal magnetic resonance imaging revealed a large mediastinal tumor of 6 cm in longitudinal diameter with encasement of adjacent mediastinal structures (Figure 2). At 29 weeks' gestation, the neonate was delivered by elective Cesarean section and intubated by ex-utero intrapartum treatment owing to fetal distress. Apgar scores were 0, 1 and 4 at 1, 5 and 10 min, respectively. The newborn was put on immediate ventilator support for severe hypoxemia, and bilateral chest tubes were inserted to drain the pleural effusions. Transthoracic sonography showed a large extracardiac mediastinal mass with compression of the left atrium. Despite the advanced medical support, the newborn developed refractory hypotension and died 2 days later. Autopsy revealed multiple cystic changes in the periventricular area of the brain (Figure S1). The mediastinal tumor was brown and soft and weighed 26.2 g with dimensions of 69 × 37 mm (Figure 3). It was found to encompass the esophagus, trachea, pulmonary trunk, aortic arch and other great vessels. Microscopic examination of the mass revealed interlacing fascicles of uniform spindle cells, with focal nuclear atypia (Figure S2). These tumor cells were diffusely positive for vimentin, focally positive for smooth muscle actin and CD68, but negative for CD31, CD34, S-100 and desmin. Tumor complementary DNA of the fusion gene transcript ETV6-NTRK3 was amplified specifically and no specific fusion gene transcripts were detected. Fluorescence in-situ hybridization revealed a wild-type EWSR1, encoding the Ewing sarcoma fusion protein, with no splitting of the alleles. The diagnosis of congenital peribronchial myofibroblastic tumor (CPMT) was made based on the myofibroblastic immunophenotype and genetic investigations (Table 1 and Table S1)123. CPMT was first defined in 1993 by McGinnis et al.4 to describe a neoplasm that develops from the embryonic pluripotent mesenchyme found surrounding large bronchi. In the past it was recognized as a malignancy or low-grade sarcoma, but it has now been categorized as a benign mesenchymal tumor with different extents of nuclear atypia. Fewer than 30 cases have been reported in the English medical literature12345. CPMT presents typically as a solid lung mass in the perinatal period, but has not been seen previously as a mediastinal tumor. Heart failure is considered the result of increased mediastinal pressure caused by encasement of the great vessels and direct cardiac compression. The clinical behaviors of CPMT are diverse, and survival rate is only 36% after excluding cases of elective termination123 5. However, patients with CPMT may have a good outcome if they can survive long enough for surgical resection5. In conclusion, when non-immune hydrops fetalis is encountered, the mediastinum should be examined carefully when other etiologies are unlikely to be the cause. Subsequent counseling and management pose more challenges than the detection of the fetal neoplasm itself. Despite its benign histopathology, CPMT in the mediastinum can have a devastating effect on the fetus because of its location and rapid growth. Y.-A. Tu†, W.-C. Lin‡, H.-J. Chen‡ and J.-C. Shih*† †Department of Obstetrics and Gynecology, National Taiwan University Hospital and National Taiwan University College of Medicine, 15F, No. 8, Chung-Shan South Road, 10002, Taipei, Taiwan; ‡Department of Pathology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan *Correspondence. (e-mail: jcshih@ntu.edu.tw) Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.