Pediatric thoracic mass lesions: Beyond the common.

Thoracic mass lesions can be categorized as originating in one of the three major compartments: a) chest wall and pleura, b) lung parenchyma and airways, c) mediastinum. While some of these, such as lymphoma, are common in both children and adults, others are rare and unique to childhood. The goal of this review is to familiarize radiologists with unusual but distinctive mass lesions of the pediatric thorax.

Introduction

The spectrum of thoracic mass lesions encountered in radiology practice differs greatly in children compared to adults. Metastases from an extra-pulmonary primary malignancy are much more common than primary pulmonary neoplasms in children. Primary pulmonary neoplasms are rare in childhood and less common than non-neoplastic conditions, such as congenital lung malformations [[1], [2], [3]]. Mesenchymal neoplasms are more common than epithelial neoplasms in the pediatric thorax, and certain neoplasms are associated with genetic disorders or infections [4].

The most common pediatric thoracic mass lesions include lymphoma, germ cell tumors, neurogenic tumors, foregut cysts, congenital pulmonary airway malformations, vascular malformations, hemangiomas, chest wall sarcomas, pleuropulmonary blastoma, inflammatory myofibroblastic tumor, endobronchial tumors, breast tumors and cardiac tumors. These have been the subject of numerous prior publications [3,[5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18]] and are beyond the scope of this review.

The aim of this review is to go beyond the common and familiarize radiologists with unusual but distinctive mass lesions involving the pediatric thorax, including certain malignant and benign neoplastic lesions and non-neoplastic proliferative and hamartomatous lesions. We will discuss these lesions based upon their primary compartmental location (chest wall/pleura, lung parenchyma/airways, mediastinum) or presumed site of origin if multi-compartmental.

Chest wall and pleura

Mesenchymal hamartoma of the chest wall

Mesenchymal hamartoma of the chest wall, also known as benign mesenchymoma, infantile osteochondroma, osteochondrosarcoma, and infantile cartilaginous hamartoma, is a benign lesion that usually presents as a deforming chest wall mass in an infant or young child [19]. This lesion accounts for 0.03 % of primary bone tumors [20]. It typically arises along the ribs and is characterized by a benign proliferation of precursors of bone tissue with a prominent cartilaginous component, oval to spindled mesenchymal cells with no atypia or abnormal mitotic activity, smooth muscle, and hemorrhagic cavities with osteoclast-like giant cells, imparting aneurysmal bone cyst-like appearance [19,21]. It may be multicentric and/or bilateral. Chest radiography (CXR) shows a partially calcified mass of the chest wall involving one or more ribs. The mass is typically well-delineated and often lobulated with bizarre remodeling or enlargement of the involved rib(s) [21]. Computed tomography (CT) (Fig. 1) and magnetic resonance imaging (MRI) may show mineralized matrix and hemorrhagic cystic components [22]. Differential diagnosis include osteosarcoma or chondrosarcoma [20]. The size of the mass may decrease even without treatment and prognosis is excellent. However, if compressive effects result in cardiac or pulmonary compromise or if the mass is physically deforming, surgical excision of the lesion is recommended [22].

Fig. 1

Mesenchymal hamartoma in an 11-month-old. Axial chest CT image in bone windows shows a lobular, well-delineated, juxtapleural mass of the posterior left hemithorax with bizarre remodeling and enlargement of the involved rib.

Periosteal chondroma

Periosteal chondroma is a benign, slow-growing tumor of hyaline cartilage developing between the cortical surface of the bone and the periosteal membrane [23]. Periosteal chondromas rarely involve a rib and may be seen both in children and adults [24,25]. Periosteal chondromas account for less than 2% of all chondromas [25]. On clinical presentation a palpable mass with swelling and pain is typically seen, but painless masses have also been described [24]. Histopathologic examination demonstrates hyaline cartilage arranged in a lobular pattern closely associated with periosteum adjacent cortical bone [24]. Radiologic correlation in these cases is imperative to avoid misdiagnosis. Radiographically, periosteal chondroma usually arises on the outer surface of a long bone and manifests as a well-delineated, lobulated, radiolucent bone surface tumor, often with calcification of the chondroid matrix and a sclerotic reaction of the cortex (Fig. 2), classically, there is a saucer-shaped erosion of the cortex with adjacent bony sclerosis [25]. Ultrasound (US), CT and MRI are helpful to demonstrate the cartilaginous tissue and its relation with the surrounding structures. On MRI, the mass is bordered by a hypointense rim, corresponding to fibrous tissue and intact periosteum [25,26]. Differential diagnosis include osteochondroma, chondrosarcoma and osteosarcoma [24]. The treatment for periosteal chondroma is surgical excision [24,25].

Fig. 2

Periosteal chondroma incidentally noted in a 6-year-old girl undergoing cardiac evaluation. (a) Frontal chest radiograph shows an opacity (arrow) projecting over the right lung. (b) Sagittal volume-rendered and (c) axial chest CT image in bone windows show a soft tissue mass (arrow) protruding from the third rib near the costochondral junction with saucerization and sclerosis of the adjacent bone.

Primitive myxoid mesenchymal tumor of infancy

Primitive myxoid mesenchymal tumor of infancy is a rare mesenchymal tumor of early childhood that can arise within the head/neck, trunk or extremities [27]. The incidence is unknown, but since it was first described in 2006, less than 20 reports of cases have been published in the literature [27,28]. The tumor is characterized on histopathology by predominantly round to bland or oval, less frequent stellate cells, and rare spindled cells in an abundant myxoid stroma with a fine "chicken-wire" vasculature [[27], [28], [29]]. Imaging findings include a heterogeneous infiltrative soft tissue mass with cystic-appearing spaces and no internal hemorrhage (Fig. 3) [27,29]. Differential diagnosis include sarcomas, myxoma, myxofibromas, and fibromatoses. The tumor has ill-defined borders with infiltration of surrounding structures. The tumor rarely metastases and has a poor response to chemotherapy; therefore, complete surgical resection is the recommended therapy, and close follow-up with serial MRI is advised to detect early recurrence [27].

Fig. 3

Primitive myxoid mesenchymal tumor of infancy in a 3-month-old girl. (a) Doppler ultrasound shows a left upper chest wall mass with vascularized solid and fluid components. (b) Contrast-enhanced axial chest CT image demonstrates a mass (arrow) of heterogenous attenuation in the left anterior chest wall abutting the left second rib and pectoralis muscle. (c) Contrast-enhanced axial T1-weighted fat sat MRI image shows a mass (arrow) in the left anterior chest wall with enhancing solid tissue and non-enhancing myxoid stroma.

Chloroma

Chloroma, also known as granulocytic (myeloid) sarcoma or extramedullary myeloid leukemia, represents a mass of leukemic cells outside the bone marrow, and is most frequently associated with acute myelogenous leukemia (AML), chronic myeloid leukemia and other myeloproliferative disorders [30]. It is a rare condition with slight male predominance and may occur at any age, more commonly in infants than in older children and at any site of the body [10,31]. However, the skin, orbits, central nervous system, and paraspinous regions are the most common sites, with occasional presentations in the chest wall adjacent to the ribs and sternum [32]. Clinical presentation is dependent on tumor location, with symptoms usually occurring as a result of a tumor mass effect or local organ dysfunction [31]. Chloromas have a strong predilection for subperiosteal and perineural involvement (Fig. 4) [32]. Histopathologic inspection shows that the tumor is composed of primitive precursors of the granulocytic series that include myeloblasts, promyelocytes and myelocytes [30]. Typical imaging findings are a high attenuation mass with intense contrast enhancement on CT, iso-/hypointensity on T1-weighted MRI, mild hyperintensity on T2-weighted MRI, and restricted diffusion on diffusion weighted imaging (DWI) due to the high cellularity [32]. Fluorodeoxyglucose-positron emission tomography (FDG-PET) is useful because of its ability to detect the lesions that are clinically occult or not detectable on conventional imaging. Increased glycolytic activity with moderate FDG uptake is typical for these cases [33]. Differential diagnosis for the imaging findings is broad and includes lymphoma and sarcomas [32]. Systemic chemotherapy should be started early, even in the nonleukemic disease stage. Surgery and/or radiotherapy may be indicated for symptomatic lesions or tumors causing local organ dysfunction or obstruction [31]. Untreated isolated chloroma ultimately transforms to AML, typically over a 10- to 12-month period [31].

Fig. 4

Chloroma in a 4-year-old boy with history of relapsed acute myeloid leukemia. (a) Contrast-enhanced axial chest CT image shows bilateral pleural effusions (*) with a rind of high attenuation soft tissue (arrows) peripheral to the effusions adjacent to the posterior ribs and thoracic spine as well as adjacent to the sternum. (b) Contrast-enhanced axial T1-weighted MRI image more clearly shows extension of the soft tissue mass (arrows) into the thoracic spinal canal with displacement of the spinal cord (*).

Lung parenchyma and airways

Infantile myofibromatosis

Infantile myofibromatosis is the most common fibrous tumor of infancy and is characterized by a benign proliferation of fibroblasts and myofibroblasts [34]. The tumor is subdivided into solitary and multicentric forms with or without visceral involvement [4,14]. Pulmonary involvement is rare, typically a manifestation of multicentric disease, and should not be misinterpreted as metastatic disease. The chest wall can also be involved [14,34]. The age of presentation is usually around 5 months for multicentric forms and 26 months for solitary forms [4]. On microscopic examination, these tumors have a nodular to multinodular proliferation with zonation, the peripheral zone of the nodule is composed of fascicles of "mature" spindled myofibroblasts without atypia or pleomorphisms, but occasional with mitotic figures. These tumor cells are embedded in a background of hyalinized to chondroid or chondromyxoid stroma. The central zone of the nodule is composed of "immature" ovoid to round spindled myofibroblasts associated with thin-walled branching vessels, imparting a hemangiopericytoma pattern [14]. On imaging, US demonstrates a thick-walled mass with an anechoic center that can resemble an abscess. On CT, the mass is nearly iso-attenuating to muscle, and on MRI the mass shows variable signal intensity on T2-weighted images with peripheral contrast enhancement (Fig. 5) [35,36]. The differential diagnosis is assisted by recognition of characteristic skeletal lesions in the multicentric form. Prognosis is worse in the multicentric forms with visceral involvement [14].

Fig. 5

Infantile myofibromatosis in a 1-month-old girl. (a) Frontal body radiograph shows a well-circumscribed left lung mass (arrow) and characteristic symmetric lucent lesions (black arrows) of the metaphyses of the lower extremity long bones. (b) Contrast-enhanced axial chest CT image shows a well-circumscribed left pulmonary mass (arrow) with an attenuation similar to skeletal muscle. (c) Axial short T1 inversion recovery(STIR) MRI image shows a well-circumscribed left pulmonary mass (arrow) that is predominantly hyperintense with a hypointense rim.

Fetal lung interstitial tumor

Fetal lung interstitial tumor is typically diagnosed in the prenatal or early postnatal period [37]. The tumor is composed of immature appearing microcystic lung tissue lined by cuboidal to low columnar epithelial cells (pneumocytes) with abundant cytoplasmic glycogen and lacking surfactant organelles. The supporting interstitial cells also contain abundant glycogen and are positive for vimentin. There are also smooth muscle cells beneath the epithelium with features resembling terminal bronchiole-alveolar ducts resemble immature fetal lung at 20–24 weeks of gestation [38,39]. Prenatal US shows a well-circumscribed, unifocal, predominantly solid lung mass with posterior acoustic enhancement (Fig. 6) [37,38,40,41]. Fetal MRI shows a well-circumscribed, intrathoracic mass that is hyperintense on T2-weighted images with radiating curved bands within and along the periphery of the lesion (Fig. 5) [37,38,41]. Fetal hydrops and heart failure are potential complications due to vena cava obstruction [41]. Findings on postnatal CXR are non-specific and include a lobar opacity with mediastinal shift [2]. Postnatal CT reveals a low attenuation mass without chest wall invasion [39]. Differential diagnosis include solid (type 3) congenital pulmonary airway malformation, congenital peribronchial myofibroblastic tumor and infantile pulmonary teratoid tumor [39]. Prognosis is favorable. Usually respiratory symptoms resolve without local recurrence or metastatic disease after surgical resection [38].

Fig. 6

Fetal lung interstitial tumor at 36 weeks gestation. (a) Prenatal ultrasound image depicts a large hyperechoic solid-appearing mass (arrows) of the right lung. (b) Coronal T2-weighted fetal MRI image shows compression of the lungs by a well-circumscribed hyperintense mass (arrows). In addition, fetal ascites (*) is noted.

Pleuropulmonary synovial sarcoma

Pleuropulmonary synovial sarcoma is a subtype of sarcoma with a distinctive chromosomal translocation involving the X chromosome and chromosome 18 (SS18-SSX1; SS18-SSX2; SS18-SSX4) specific to synovial sarcoma [[42], [43], [44]]. It predominantly affects adolescents and young adults and represents 0.1−0.5% of all primary pulmonary malignancies [43]. Histologically, synovial sarcoma occurs in two different patterns: monophasic and biphasic. Monophasic synovial sarcoma is composed of malignant plump fusiform cells that are closely attached to one another, in a vague fascicular pattern with minimal stroma. Biphasic synovial sarcoma is composed of similar fusiform cells with area of gland-like epithelial structures lined by round to ovoid tumor cells [43,44]. On imaging, CXR typically shows a well-defined round or oval soft tissue mass of the lung or pleura, and is often accompanied by an ipsilateral pleural effusion [43]. CT reveals a well-circumscribed heterogeneously enhancing soft tissue mass without bone involvement or calcifications (Fig. 7) [45]. MRI provides superior demonstration of the enhancing nodular soft tissue component and multilocular fluid-filled component of the mass [43,46]. Differential diagnosis includes type II (mixed solid-cystic) pleuropulmonary blastoma, superinfected congenital lung malformation, and other sarcomas [4]. Current treatment consists of surgical resection followed by chemotherapy, radiotherapy, or both [43].

Fig. 7

Pleuropulmonary synovial sarcoma in a 13-year-old boy. (a) Frontal chest radiograph shows a large lobular mass (arrows) within the left mid and lower hemithorax obscuring the silhouette of the left heart border and hemidiaphragm. (b) Contrast-enhanced axial chest CT image demonstrates a large lobular mass (*) of heterogeneous attenuation abutting the cardiomediastinal structures and extending across the left hemithorax from the anterior to posterior pleura.

Leiomyoma and leiomyosarcoma

Leiomyoma and leiomyosarcoma of the pediatric lower respiratory tract are tumors of smooth muscle origin that exist along a benign to malignant spectrum and are associated with Epstein-Barr virus (EBV) infection and immunosuppressed states [47]. Patients usually present with nonspecific respiratory signs and symptoms [4]. Histologically, smooth muscle tumors are characterized by spindle cells with prominent eosinophilic cytoplasm, blunt end nuclei, and deep wrinkling of the nuclear membranes secondary to contraction artifact of the myofilaments during fixation. There is minimal cytologic atypia and rare to absent mitotic figures. The tumor cells occur in bundles or vague fascicles, and are closely apposed with minimal stroma. Transformation to malignant leiomyosarcoma is characterized by increased cellularity, marked pleomorphism, increased mitotic activity and invasion into adjacent tissues [14]. On imaging studies (Fig. 8) these tumors most commonly present as well-defined solid pulmonary or endobronchial masses [4]. These smooth muscle tumors are typically indolent and treated with surgery, chemotherapy or reduction in immunosuppression [47].

Fig. 8

Leiomyomas in an 11-year-old boy with history of acquired immunodeficiency syndrome (AIDS). Contrast-enhanced axial (a,b) chest CT images in lung windows and coronal (c,d) chest CT images in lung and soft tissue windows demonstrate multiple well-defined nodular pulmonary masses (black arrows) representing leiomyomas, as well as hyperlucent foci related to cystic lymphocytic interstitial pneumonia.

Mediastinum

Thymic Langerhans cell histiocytosis

Langerhans cell histiocytosis (LCH) is a rare disorder of unclear etiology characterized by proliferation and tissue infiltration by Langerhans cells with accompanying local and systemic inflammation [48,49]. The incidence of LCH is 2.6–5.4 cases per million children [50]. LCH presents a diagnostic challenge because it may manifest with a heterogeneous spectrum of lesions, ranging from a single bone lesion to multisystem disease. The thymus is commonly involved in pediatric LCH, especially in multisystem disease [51,52]. However, isolated thymic disease has rarely been reported in the literature [53]. Histologically, Langerhans cells are highly differentiated histiocytes of the stellate dendritic antigen-presenting cell lineage. The hallmark of LCH is an uncontrolled monoclonal proliferation of abnormal Langerhans cells, which may infiltrate nearly any tissue or organ as well as lymph nodes. This histiocytic infiltration is accompanied by chronic inflammation and the formation of granulomas [50]. On imaging, thymic involvement manifests as an enlarged thymus with or without cysts and amorphous calcifications on CXR or CT (Fig. 9) [51,52,54] and with heterogeneous uptake on FDG-PET [53]. US is an alternative method of assessing thymic involvement in patients younger than 2 years [51]. Differential diagnostic considerations of thymic LCH include lymphoma, germ cell tumor, juvenile xanthogranuloma and other forms of non-Langerhans cell histiocytosis [4,50]. Chemotherapy is the current standard of care for multisystem LCH, although progression-free survival among high-risk patients remains less than 50 % [49]. Children with liver, spleen, or bone marrow involvement are at highest risk for death from LCH [49].

Fig. 9

Langerhans cell histiocytosis in a 3-month-old boy with history of cough and poor feeding. (a) Frontal and (b) lateral chest radiographs show a large mass (arrows) within the anterior mediastinum obscuring the silhouette of the upper heart border. (c) Non-contrast axial chest CT image shows a large anterior mediastinal mass with multiple amorphous calcifications. (d) Axial chest CT image in lung windows shows multiple cystic lung lesions (arrows).

Kaposiform hemangioendothelioma

Kaposiform hemangioendothelioma is a locally aggressive vascular proliferation associated with Kasabach-Merritt phenomenon [55]. It occurs predominantly in infants and young children, most commonly as a superficial or deep soft tissue mass of the extremities or trunk, but may also occur in the head/neck, mediastinum, or retroperitoneum [[55], [56], [57], [58], [59]]. The risk of Kasabach-Merritt phenomenon increases dramatically when there is involvement of the mediastinum, retroperitoneum or muscle [58]. On histopathologic examination, the tumor is biphasic and composed of vascular and lymphatic components with irregular nodules of convoluted vessels and associated dense hyalinized stroma. The vessels are often associated with epithelioid and glomeruloid endothelial cell islands, resembling capillary hemangioma and Kaposi sarcoma. Hemosiderin deposition and fibrin thrombi are typically present [55]. On CT or MRI, Kaposiform hemangioendothelioma typically appears as an enhancing, infiltrative soft tissue mass with adjacent edema (Fig. 10) [59,60]. Differential diagnosis includes hemangioma and sarcomas. Intravenous corticosteroids, beta blockers, vincristine have proven to be effective [55].

Fig. 10

Kaposiform hemangioendothelioma in a 4-year-old boy with Kasabach-Merritt syndrome. Contrast-enhanced (a) coronal, (b) sagittal, and (c) axial T1-weighted fat saturated MRI images demonstrate a poorly-defined enhancing soft tissue mass (arrows) infiltrating the lower mediastinum and upper retroperitoneum.

Kaposiform lymphangiomatosis

Kaposiform lymphangiomatosis is an aggressive lymphatic disorder [61]. The mediastinum is involved in all thoracic cases, with the lungs and pleura also frequently involved. The age at presentation ranges from 3 months to 27 years [61]. The most common presenting symptom is respiratory compromise [61]. Histologically, it is characterized by clusters or sheets of spindled lymphatic endothelial cells accompanying malformed lymphatic channels that immunoreact with D240 [62]. The imaging features of Kaposiform lymphangiomatosis overlap with central conducting lymphatic anomaly and generalized lymphatic anomaly. On CT and MRI there is typically a mediastinal or retroperitoneal enhancing, infiltrative soft tissue lesion along the lymphatic distribution (Fig. 11) [61]. The mortality rate is high despite aggressive multi-modal therapy [62].

Fig. 11

Kaposiform lymphangiomatosis in a 6-year-old boy. (a) Frontal chest radiograph shows mediastinal widening and parahilar interstitial thickening. (b) Contrast-enhanced axial T1-weighted fat sat MRI image reveals extensive infiltration (arrows) of the mediastinum by enhancing soft tissue.

NUT carcinoma

NUT carcinoma (formerly NUT midline carcinoma) is a highly aggressive, poorly differentiated subtype of squamous carcinoma characterized by a translocation resulting in NUT oncogene overexpression [2,4,39,63]. It affects male and female patients equally, with a wide age distribution [63,64]. NUT carcinoma most commonly arises from the midline head/neck or mediastinum [64].The presenting symptoms are nonspecific and vary depending on the primary site of tumor or the presence of metastases [39]. Pleuritic chest pain, weight loss, non-productive cough and shortness of breath are common when NUT carcinoma arises from thorax [65]. This entity is defined by rearrangement of the NUT gene (chromosome 15q14) with BRD4 (chromosome 19p31), most often, and on occasion with BRD3 (chromosome 9q34.2) [64]. Undifferentiated epithelioid to round cells with variable squamous differentiation are characteristic for this neoplasm, and there may be a degree of desmoplasia [63,64]. CT imaging demonstrates a heterogeneous mass with central necrosis and occasional calcifications (Fig. 12) [[65], [66], [67]]. On MRI, the tumor is hypointense on T1-weighted images, slightly hyperintense on T2-weighted images, and heterogeneously enhancing on post-contrast T1-weighted images [67]. FDG-PET is the imaging modality of choice for assessing for metastatic disease [66]. The lungs are the most common site of metastases and metastases to the liver, kidney, brain, spinal cord and subcutaneous soft tissues have been reported [4]. Differential diagnosis includes tuberculosis, histoplasmosis, neuroblastoma, lymphoma, sarcoma and IgG4-related disease. NUT carcinoma is almost always lethal [64].

Fig. 12

Nuclear protein of the testis (NUT) carcinoma in a 12-year-old boy with a history of non-productive cough and weight loss. (a) Frontal chest radiograph demonstrates leftward displacement of the trachea by a right paratracheal mass (arrows), narrowing of the left mainstem bronchus, a right infrahilar mass (arrows) and a right pleural effusion (*). Contrast-enhanced (b) coronal and (c) axial CT images reveal centrally necrotic masses (arrows) in the paratracheal, subcarinal, right hilar and peribronchial nodal regions.

Conclusion

Awareness of the spectrum of thoracic mass lesions is essential to provide optimal care for pediatric patients. In addition to common entities, there are less common malignant and benign neoplastic, non-neoplastic proliferative and hamartomatous lesions that may arise from the chest wall, lungs, or mediastinum. Differential diagnosis is aided by recognition of their typical age distribution, presenting signs and symptoms, site of anatomic origin, and imaging features.

Declaration of Competing Interest

This manuscript is the original work of all authors, no part of this article has been published or presented before, nor is any part of it under consideration for publication elsewhere. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. There are no conflicts of interest to disclose. All authors have read and approved the final version of the manuscript.