Congenital Peribronchial Myofibroblastic Tumor Research Articles

Fetal Lung Interstitial Tumor (FLIT): Review of The Literature.

Fetal lung interstitial tumor (FLIT) is an extremely rare pediatric lung tumor that shares radiological features with congenital pulmonary malformations (cPAM) and other lung neoplasms. A review of the literature, together with the first European case, are herein reported. A systematic and manual search of the literature using the keyword "fetal lung interstitial tumor" was conducted on PUBMED, Scopus, and SCIE (Web of Science). Following the PRISMA guidelines, 12 articles were retrieved which describe a total of 21 cases of FLIT, and a new European case is presented. A prenatal diagnosis was reported in only 3 out of 22 (13%) cases. The mean age at surgery was 31 days of life (1-150); a lobectomy was performed in most of the cases. No complications or recurrence of disease were reported at a mean follow-up of 49 months. FLIT is rarely diagnosed during pregnancy, may present at birth with different levels of respiratory distress, and requires prompt surgical resection. Histology and immunohistochemistry allow for the differentiation of FLIT from cPAM and other lung tumors with poor prognosis, such as pleuropulmonary blastoma, congenital peri-bronchial myofibroblastic tumor, inflammatory myofibroblastic tumor, and congenital or infantile fibrosarcoma.

Congenital peribronchial myofibroblastic tumor (CPMT): a case report with long term follow-up and next-generation sequencing (NGS)

BackgroundCongenital peribronchial myofibroblastic tumor (CPMT) is an extremely rare lung disease in infants. It shows benign behavior and has a favorable survival after surgical treatment. CPMT was reported only in cases. Here, we report the longest follow-up known case of CPMT and review the clinical, radiographic and histopathological features of the published literature.Case presentationUltrasound examination at 30 weeks of gestational age of a healthy 29-year-old female revealed a solid mass in the left lung. Computed tomography (CT) revealed a mass in the left lower lobe. The tumor was removed by lobectomy and pathologically diagnosed with CPMT. The tumor was composed of cartilage, spindle cells and oval cells. Vimentin was strongly positive. Smooth muscle actin (SMA) was positive in the spindle cells. The histopathologic and immunohistochemical features were similar to those in the literature. No ETV6-NTRK3 fusion or ALK rearrangement was detected. Gene mutations in JAK2 and SMO were detected by NGS. She is currently alive for 8 years with no evidence of disease recurrence.ConclusionsCPMT is a rare lung tumor in infants. Surgical treatment is recommended for CPMT. The prognosis after successful surgery is favorable. The final diagnosis was histopathologic findings. Due to its cellularity, mitotic activity and rapid growth, long-term follow-up should be strengthened. The present patient is alive and well for 8 years after the surgery without recurrence. Gene mutations in JAK2 and SMO were detected, which may be associated with the formation of CPMT.

The rare solid fetal lung lesion with T2-hypointense components: prenatal imaging findings with postnatal pathological correlation.

At fetal MR, congenital lung lesions are usually T2 hyperintense with respect to normal lung parenchyma. Some lesions, however, demonstrate unusual patterns of T2 hypointensity, sometimes in a rosette-like pattern. These lesions usually present a diagnostic conundrum. To evaluate the imaging findings and pathological characterization of fetal solid lung lesions with elements showing T2-hypointense signal with respect to lung. This is a retrospective study of lung lesions with elements showing T2 hypointensity treated prenatally and postnatally at our center and with available pathological evaluation. Prenatal imaging evaluation included US and MR; postnatal evaluation consisted of pathological examination of the lesion. We also performed prenatal and postnatal chart review. Six cases met study criteria. Areas of decreased echogenicity/T2-hypointense signal were more conspicuous at MR than US. At pathology, these areas correlated with immature parenchymal development and increased mesenchymal tissue. Five of these lesions were congenital pulmonary airway malformations (CPAM); one was a congenital peribronchial myofibroblastic tumor (CPMT). The lesions did not significantly change in size after steroid administration. They were all large in volume and were associated with increased amniotic fluid. All cases of CPAM underwent premature delivery (one of them weeks after fetal surgical resection of the lesion for worsening hydrops); the fetus with CPMT was delivered at term. The neonate with CPMT succumbed shortly after birth secondary to lung hypoplasia; the remaining five neonates survived. The differential diagnoses of prenatal lung lesions that contain unusual T2-hypointense elements include CPAM and CPMT. The T2-hypointense areas appear to correlate with increasing degree of immaturity at histology. None of the lesions significantly changed in size after prenatal administration of steroids. All cases with CPAM lesions did well despite persistent polyhydramnios and premature birth. The single case of CPMT, however, resulted in neonatal demise shortly after birth secondary to pulmonary hypoplasia. It is important that fetal radiologists, obstetricians and fetal surgeons alike are aware of these lesions so that appropriate diagnosing and parental counseling can be reached.

Neonatal congenital lung tumors - the importance of mid-second-trimester ultrasound as a diagnostic clue.

The differential diagnosis for primary lung masses in neonates includes a variety of developmental abnormalities; it also consists of the much rarer congenital primary lung tumors: cystic pleuropulmonary blastoma (cystic PPB), fetal lung interstitial tumor (FLIT), congenital peribronchial myofibroblastic tumor (CPMT), and congenital fibrosarcoma. Radiologic differentiation between malformations and tumors is often very challenging. The objective was to establish distinctive features between developmental pulmonary abnormalities and primary lung tumors. We conducted a retrospective study of 135 congenital lung lesions at a university mother and child center over a period of 10years (2005-2015). During this time, we noted four tumors (two cystic PPBs and two FLITs) and 131 malformations. We recorded the following parameters: timing of conspicuity in utero (mid-second trimester, third trimester, or not seen prenatally), presence of symptoms at birth, prenatal and perinatal radiologic findings, and either histological diagnoses by pathology or follow-up imaging in non-operated cases. All lesions except the four tumors were detected during mid-second-trimester ultrasound. In none of the tumors was any pulmonary abnormality found on the mid-second-trimester sonogram, contrary to the developmental pulmonary abnormalities. The timing of conspicuity in utero appears to be a key feature for the differentiation between malformations and tumors. Lesions that were not visible at the mid-second-trimester ultrasound should be considered as tumor. A cystic lung lesion in the context of a normal mid-second-trimester ultrasound is highly suggestive of a cystic PPB. Differentiating the types of solid congenital lung tumors based upon imaging features is not yet feasible.

Prenatal imaging and immunohistochemical analysis of congenital peribronchial myofibroblastic tumor

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.

Congenital peribronchial myofibroblastic tumor: Case report and review of literature

Congenital peribronchial myofibroblastic tumor (CPMT) is a rare entity recognized in the WHO classification of pulmonary neoplasms. According to available literature, it is a benign tumor with a high mortality rate exceeding 50%. It is partially attributed to polyhydramnios, hydrops, prematurity, respiratory distress or adverse surgical outcomes due to intraoperative bleeding. Herein we present a case of congenital peribronchial myofibroblastic tumor in a premature male infant who was born at 31 weeks gestation due to polyhydramnios and premature rupture of membranes. Soon after birth, he required intubation due to worsening respiratory distress. Imaging demonstrated a large right chest mass causing mediastinal shift. Surgical intervention was attempted, which was challenging due to intraoperative bleeding and tumor retraction. The patient expired soon after the surgery. Hence, in this report we would like to share our experience with this difficult diagnosis and treatment of this rare tumor. • CPMT is a rare benign pulmonary neoplasm usually affecting fetuses in the 3rd trimester and young newborns. • Symptoms of CPMT include polyhydramnios, non-immune hydrops, premature rupture of membranes and respiratory distress. • The mortality rate of CPMT exceeds 50%. • Complications of surgical resection include massive perioperative bleeding and respiratory insufficiency. • The most important differential diagnostic consideration is solid CPAM.

Congenital peribronchial myofibroblastic tumor: prenatal imaging clues to differentiate from other fetal chest lesions

We present a prenatal case of congenital peribronchial myofibroblastic tumor referred as a congenital pulmonary airway malformation (CPAM) with hydrops and polyhydramnios at 30 weeks' gestational age. US and fetal MRI findings did not fit with the referral diagnosis, raising the possibility of intrinsic lung tumor. Fetal hydrops worsened and the baby was successfully delivered by ex utero intrapartum treatment (EXIT) to resection at 31 weeks' gestational age. To the best of our knowledge, this is a unique case of congenital peribronchial myofibroblastic tumor that underwent comprehensive prenatal evaluation and EXIT procedure with good outcome.

Congenital peribronchial myofibroblastic tumor: a case report and review of the literature.

Congenital peribronchial myofibroblastic tumor is a rare, solid mesenchymal tumor of the neonate, usually associated with non-immune hydrops fetalis. We present a case of congenital peribronchial myofibroblastic tumor, in whom a right lung mass was detected in intrauterine life. 12 days after delivery by caesarean section, right lobectomy was performed. The tumor was limited to the lung, and was composed of spindle cells, proliferating around a bronchial unit. Central necrosis and 4-5 mitoses per 10 high power fields were present. The patient is well 26 months after surgery. We report this rare tumor with clinical, radiological and pathologic findings and a review of the literature.

Congenital Peribronchial Myofibroblastic Tumor: A Case Study and Literature Review

Congenital peribronchial myofibroblastic tumor (CPMT) is a benign pulmonary spindle cell neoplasm of intrauterine and perinatal period, which is thought to arise from primitive peribronchial mesenchyme. We present a case detected incidentally in a one-month-old infant. The solid and partially necrotic tumor involved the right middle and lower lobes of the lung with extension to the diaphragm. Histologically, the tumor was composed of fasciculated monotonous spindle cells, proliferating peribronchiolar cartilage and round cells with rich vasculature, and high mitotic activity was identified in the round cell area. Immunohistochemical and electron microscopic studies showed that the spindle cells were myofibroblastic in phenotype. Although the tumor showed several malignant pathological features, recurrence was not observed in the two-year follow-up period, consistent with the benign clinical behavior of CPMT.

Congenital Peribronchial Myofibroblastic Tumor: Comparison of Fetal and Postnatal Morphology

Congenital peribronchial myofibroblastic tumor (CPMT) is a solid pulmonary tumor found in fetuses and neonates with pathology characterized by a proliferation of bland spindled cells with or without irregular cartilaginous islands. It has previously been reported in the literature as a fibrosarcoma, leiomyosarcoma, and hamartoma, among other names. Although complications such as fetal hydrops can occur, the prognosis is generally good if the infant can survive long enough for mass resection. We present a case of a CPMT resected by antenatal fetal surgery at 23 weeks in gestation, with additional tumor resected following birth when the infant was 6 weeks of age. The pathology of this lesion showed a marked increase in the cartilaginous component after birth as well as a decrease in cellularity and mitotic activity. This case presents a unique opportunity to examine the progression of a congenital tumor excised by prenatal and postnatal resections.

Fetal Lung Interstitial Tumor (FLIT)

The differential diagnosis of congenital lung lesions includes a variety of pulmonary malformations, and uncommon or rare neoplasms such as the pleuropulmonary blastoma (PPB) and congenital peribronchial myofibroblastic tumor (CPMT). Although most of the congenital lesions have a predominantly cystic appearance, the exceptions of a more solid process are the type 3 congenital cystic adenomatoid or pulmonary airway malformation (CCAM-CPAM) and the CPMT. The clinical and pathologic features of a unique solid or mixed solid/cystic lung mass composed of immature interstitial mesenchyme in association with irregular airspace-like structures mimicking abnormal incompletely developed lung are presented in this report of 10 infants (7 males, 3 females) whose tumor-like lesions were detected in the prenatal period to 3 months of age (median, 1-day old). A lobectomy was done in all 10 infants and 1 infant received adjuvant chemotherapy. One of the surgical resections occurred as an ex utero, antenatal procedure because of fetal ascites. There have been no reported recurrences in those patients with greater than 12 months of follow-up ranging from 15 to 182 months (9 cases). Because of the morphologic resemblance of this mass-like lesion to fetal lung at 20 to 24 weeks gestation (as though any further pulmonary development was arrested in these localized lesions), we are proposing the designation of fetal lung interstitial tumor (FLIT) whose pathogenetic relationship, if any, to type 1 (cystic) pleuropulmonary blastoma remains uncertain to date.

Congenital Peribronchial Myofibroblastic Tumor: A Case Report

We describe a rare occurrence of congenital peribronchial myofibroblastic tumor of the lung presenting in early fetal life. A female patient in the 24th week of gestation who presented with polyhydramnios was admitted for examination. Ultrasound examination revealed a mass compromising the lungs. Because the intrauterine fetal death was revealed by the ultrasound, delivery was induced. Necropsy revealed a pulmonary lesion compromising the left lower pulmonary lobe together with hepatomegaly. Microscopic analysis of the lung showed a lesion with a storiform arrangement of spindle cells with focal peribronchial distribution. Hepatic architecture was diffusely altered by fibrotic tissue. Immunohistochemical analysis on the pulmonary lesion showed high vimentin positivity in the fusocellular components, pointing to the mesenchymal nature of the lesion. Significant differentiation of smooth muscle tissue, as indicated by high HHF35 positivity, was also observed. Electron microscopy on the pulmonary lesion revealed elongated cells with some cytoplasmatic processes, a finding that is also compatible with mesenchymal differentiation.

Primary and Metastatic Lung Tumors in the Pediatric Population: A Review and 25-Year Experience at a Large Children's Hospital

Primary lung neoplasms are rare in children, but they comprise a broad and interesting spectrum of lesions, some of which are familiar from other tissue sites, and some of which are unique to the pediatric lung. To determine the relative incidence of primary and metastatic lung tumors in children and adolescents through a single-institution case series, to compare these data to reports in the medical literature, to discuss the clinical and pathologic features of primary tumors of the tracheobronchial tree and lung parenchyma in children, and to provide recommendations for handling pediatric lung cysts and tumors. A 25-year single institutional experience with pediatric lung tumors, based on surgical biopsies and resections at Texas Children's Hospital from June 1982 to May 2007, an additional 40 lung tumors referred in consultation, and a review of the medical literature. A total of 204 pediatric lung tumors were diagnosed at our institution, including 20 primary benign lesions (9.8%), 14 primary malignant lesions (6.9%), and 170 secondary lung lesions (83.3%). The ratio of primary benign to primary malignant to secondary malignant neoplasms is 1.4:1:11.6. The common types of lung cancer in adults are exceptional occurrences in the pediatric population. The most common primary lung malignancies in children are pleuropulmonary blastoma and carcinoid tumor. Other primary pediatric lung tumors include congenital peribronchial myofibroblastic tumor and other myofibroblastic lesions, sarcomas, carcinoma, and mesothelioma. Children with primary or acquired immunodeficiency are at risk for Epstein-Barr virus-related smooth muscle tumors, lymphoma, and lymphoproliferative disorders. Metastatic lung tumors are relatively common in children and also comprise a spectrum of neoplasia distinct from the adult population.