Congenital Peribronchial Myofibroblastic Tumor: A Rare Tumor of the Fetus or Neonate

With the exception of developmental malformations, primary lung masses in the fetus/neonate are rare. Differentials include benign lesions(fetal lung interstitial tumor (FLIT), infantile myofibromatosis (IMT), CPMT and vascular or lymphatic lesions)and malignant tumors including pleuropulmonary blastoma (PPB) and infantile fibrosarcoma[2-5].There are few published reports of CPMT, with approximately 25 English case reports [1,6]. CPMT, initially described as a hamartoma of the lung in 1949 [7], wasre named CPMT in 1993 [8,9]. It arises at approximately 12weeks of gestation from the peribronchialpluripotent mesenchyme, and thus shares a similar pathogenesis with other mesenchymal lesions of the lung[2, 3].

Histologically, the tumor demonstrates bland spindle cell proliferation(myofibroblasts) with variable amounts of irregular cartilaginous islands that track along bronchi, infrequent to variable mitotic activity without cytologic atypia, occasional cystic/necrotic areas and prominent vascularity[2]. Immunohistochemical staining may bepositive for vimentin,likely reflecting the tumor’s mesenchymal origin[1]. Actin smooth muscle stain may be positive while desminstains (striated muscle) are usually negative. Electron microscopic studies show myofibroblastic differentiation [9]. Our cases were both actin positive and desmin negative.

A few single cases reports have included isolated tumoral genetic abnormalities (JAK2 and SMO) in the tumor[1].  In case 2, an EFGR KDD genetic mutation was identified at the time of percutaneous needle biopsy. Three additional prior pathologically proven cases of CPMT (two from another outside institution) have been retrospectively evaluated and were similarly positive for this genetic abnormality [10]. Of note, this mutation has also been described in congenital mesoblastic nephroma (CMN), a tumor morphologically and clinically very similar to CPMT, suggesting that CPMT and CMN may be related neoplastic variants occurring at different sites[10]. Additionally, EFGR KDD has been found in an unusual soft tissue infantile fibrosarcoma that shares morphologic characteristics with CMN[11]. The significance of this genetic finding is unknown, but it may prove to be a useful marker for identifying CPMT.

As in the cases we present, CPMT usually presents in the late prenatal or early postnatal period and is often large at presentation. Hydrops fetalis has been reported [5,12]and fetal demise may occur due to cardiovascular failure from cardiac compression or rarely mediastinal encasement of the great vessels[2,6,13].Postnatal respiratory compromise is frequent.  There is no gender, side or lobe predilection [2].Our cases included 1female and 1 male; both masses were right sided; one predominantly right lower and one right upper lobe. Resection has been curative, with lobectomy or pneumonectomy often required due to the large size and location of the lesion. There have been no reports of recurrenceor metastasis[2].

Due to its rarity, CPMT is often misdiagnosed in utero and/or postnatally. Original imaging diagnoses in our cases included CPAM and malignant neoplasm.

Consideration of this diagnosis is important for appropriate prenatal monitoring and postnatal management. The timing of lesion conspicuity on US is helpful in distinguishing between the various pulmonary entities that may be seen prenatally. Additionally, several imaging characteristics may be useful. On prenatal US,CPMT is most often (though not always) first identified during the late second trimester at approximately 28weeks, while congenital pulmonary abnormalities are typically seen earlier around 22 weeks[14]. In contrast, other pulmonary neoplasms usually present in the third trimester or postnatally. Unlike typical CPAMs which are relatively homogeneous on prenatal sonography and typically peak in size at 20-26weeks, CPMT is characteristically heterogeneous on imaging and often demonstrates rapid growth in late gestation/neonatal period [2,14]. CPMT lesions are typically round to oval in shape and mass-like in appearance, whereas congenital lung malformations tend to have the shape of a lung lobe or lobule[12].  One of the most helpful features in differentiating CPMT from a congenital developmental abnormality of the lung or other neoplasms is its hypervascularity, readily apparent on imaging(Fig1a,1d,2b, 2d)[12-15]. While atypical CPAMs may have increased vascularity on US [16], hypervascularity is unusual and should raise the possibility of an alternative diagnosis. Of note, the vascular supply of a CPMT arises from the pulmonary artery. A systemic feeding artery is not a feature of CPMT and when present, suggests sequestration rather than CPMT[12].

On fetal MRI, CPMT is often T2 hypointense to surrounding fetal lung, but, as in the cases shown, signal intensity both pre- and postnatally may be variable (Fig1b,2c).Cystic or necrotic areas may be present [2,14].

The presence of air bronchograms, seen within the tumor in both our cases on post-natal imaging is a useful unusual feature of CPMT (Fig1d, 2b,2c);and is not present in most malignant tumors (lymphoma being the exception) or congenital lung malformations. This feature may reflect the peribronchial origin and growth of this lesion along bronchi rather than displacing or compressing them. The peribronchial nature of this neoplasm on pathology is well recognized; however, to our knowledge, the description of prominent air bronchograms within the lesion on imaging has only been mentioned in one prior case [2].