Pleuropulmonary blastoma is a rare, primitive primary neoplasm of the thorax in young children. The tumor, which is often but not always associated with cystic lung lesions, may arise in pulmonary parenchyma, the mediastinum, and pleura. Histologically, it is characterized by a biphasic neoplastic population of undifferentiated-appearing small round cells and larger spindle-shaped cells. A proportion of these cancers may also manifest more specific mesenchymal differentiation. In contrast to the pulmonary blastoma of adults, a malignant epithelial component does not occur. We present herein the third known case of a fine needle aspiration biopsy of a pleuropulmonary blastoma in a 5-year-old girl. The smears were moderately cellular and included an admixture of the characteristic small ovoid blastemal elements and scattered spindled mesenchymal tumor cells.
Distinct from pulmonary blastoma, the pleuropulmonary blastoma (PPB) is an extremely uncommon primary embryonal mesenchymal malignant neoplasm that occurs in young children.1–3 These tumors may arise within pulmonary parenchyma, in association with the pleura, or within the mediastinum. Grossly, the neoplasms may appear largely cystic, solid, or mixed. Histologically, an admixture of primitive blastemal cells and spindle-shaped sarcomatous elements is present. Malignant epithelial cells are not present, a key morphologic point in differentiating PPB from the adult pulmonary blastoma.
Although its histopathologic structure has recently been well characterized in several series,1–3 we are aware of only 2 prior case reports of the aspiration cytomorphologic structure of PPB.4,5 We describe a young girl who initially presented when younger than 2 years with cystic lung lesions. Although the cystic PPB typically manifests rhabdomyosarcomatous cells in a cambium layer beneath the benign respiratory epithelium, we did not find this in our cystic component. Three years later, solid tumor masses were aspirated and then surgically resected.
REPORT OF A CASE
A 21-month-old, previously healthy girl presented initially with a generalized rash and nonproductive cough, which progressively became croupy with moderate stridor. A chest x-ray film demonstrated a thick-walled cystic lesion in the right lung, which enlarged within a month with mediastinal compression. Surgical resection of a cystic right middle lobe and a wedge resection of the right lower lobe were performed. The histologic diagnosis was multilocular congenital pulmonary cyst. For 3 years, her condition had an uneventful course. At the age of 5 years, she presented with persistent cough, and a chest x-ray film demonstrated a 3.0- × 2.5-cm mass in the right middle lung field. A fine needle aspiration biopsy (FNAB) was performed. This was followed by a wedge resection of a 3.0-cm cystic mass of the right upper lobe. The diagnosis was pulmonary blastoma associated with a cystic malformation; this patient was seen 8 years before the publication of the article by Manivel et al.1 One year later, she presented with cough and a mass involving the soft tissues of the anterior right chest wall. A FNAB yielded a diagnosis of recurrent pulmonary blastoma. The patient underwent multiple chemotherapy and radiation protocols, but she died 2 years after the diagnosis of blastoma.
When the patient was 21 months old, the surgical resection specimens revealed multiloculated cysts up to 5.0 cm in diameter, which were in continuity with the pleural surface. Microscopically, flattened and hypertrophied type II pneumocytes lined the cysts (Figure 1). Their walls consisted of vascular fibrous connective tissue that did not contain obvious malignant cells.
When the patient was 5 years old, the first FNAB of the mass on the right middle lung field provided a cellular sample with numerous single and aggregated tumor cells (Figure 2). Most were mononucleated, but rare binucleated forms were also evident. The nuclei were round to oval with finely granular, evenly distributed hyperchromatic chromatin. One or 2 nucleoli were often visible in many cells. Their cytoplasm was scanty, resulting in high nuclear-cytoplasmic ratios. A less frequent second cellular population consisted of elongated spindle-shaped cells with similar-appearing nuclei. There was no evidence of neoplastic epithelium within the smears. The aspiration diagnosis was “small cell malignant neoplasm; rule out metastatic neuroblastoma or sarcoma.”
This was immediately followed by a right upper lobe resection, which yielded a 3.0-cm cystic mass of tan tissue that included cartilaginous material. Histologically, the blastomous tumor cells were present in diffuse sheets, which focally formed malignant cartilage (Figure 3). In addition, more loosely arrayed, elongated spindled tumor cells were present.
The cytomorphologic findings of the second FNAB (when the patient was 6 years old) resembled the first. A thoracentesis yielded cloudy fluid that contained scattered clusters of malignant blastemal elements.6
In 1998, Manivel et al separated the clinicopathologic entity PPB from the more common, although still rare, pulmonary blastoma.1 Subsequent work has supported the concept of the PPB as a specific primitive embryonal malignant neoplasm that occurs almost exclusively in young children.2,3 In contrast to the pulmonary blastoma, which almost always originates within the lungs of adults, the PPB arises not only within pulmonary parenchyma but also in association with the pleura and mediastinum. Recently, Novak et al demonstrated that trisomy 8 is a karyotypic abnormality associated with PPB.7 Overall, the prognosis is dismal.3
The characteristic histopathologic component of PPB includes a biphasic cellular proliferation. One component consists of primitive cells with solitary round hyperchromatic nuclei, at times with distinct nucleoli and scanty cytoplasm, resulting in high nuclear-cytoplasmic ratios. The other major neoplastic element is a spindle-shaped mesenchymal cell. By definition, epithelial cells are not a component of this tumor. If present, they represent entrapped benign mesothelium or epithelium. In many instances, focal mesenchymal differentiation is recognized as chondrosarcomatous, liposarcomatous, and especially rhabdomyosarcomatous elements.
The cytomorphologic findings of FNAB of PPB may recapitulate any or all of its histopathologic components. In our experience, the two major cell types—the primitive blastemal elements and spindle-shaped cells—were represented in the aspiration smears. The former manifested no recognizable differentiation and readily fell into the differential diagnosis of the small round cell tumors of childhood. The blastemal component presented in the smears as both individual cells and cohesive aggregates. Within the latter, no evidence of an orderly arrangement was seen, although nuclear molding was apparent. The more elongated or spindle-shaped component had ovoid hyperchromatic nuclei and long, thin, tapering cytoplasmic tails. The spindled mesenchymal component presented mostly as individually dispersed tumor cells. Our specimens did not demonstrate any specific mesenchymal differentiation. In the initial report by Gelven et al, these same cellular elements were found in their aspiration smears but in addition included some chondroid matrix.4 The subsequent report by Drut and Pollono furtherincluded pleomorphic tumor giant cells (some multinucleated) and myxoid matrix material.5 The pleural fluid sample from our patient contained rare, small clusters of primitive blastemal cells, resembling those seen in the aspiration biopsy specimens.6 No specific differentiation was recognizable.
The differential diagnosis in cytologic preparations includes predominantly other tumors in the small round cell category.8 Of the primary neoplasms, the primitive neuroectodermal tumor arising within thoracic soft tissue is a serious consideration. The small primitive neoplastic cells from the two may be indistinguishable in smears. Rosettelike structures may be associated with primitive neuroectodermal tumor, which may also show fibrillar background material. Lymphoblastic lymphoma needs to be considered in PPB arising within the mediastinum. Aspirates of this lymphoma are usually highly cellular, consist of numerous individually dispersed small lymphoblasts, and include numerous lymphoglandular bodies in the background. The lymphoblasts are characterized by delicate, irregular nuclear membranes, fine powdery chromatin, and inconspicuous nucleoli. Tumors metastatic to the lung and pleura also need to be considered. Foremost among these would be metastatic neuroblastoma and embryonal rhabdomyosarcoma. In addition to primitive neuroblasts, aspirates of neuroblastoma may include larger neoplastic ganglion cells, pseudorosettes, and filamentous background material. Embryonal rhabdomyosarcoma may be difficult to distinguish from a PPB in an aspirate, especially if the PPB manifests a prominent rhabdomyosarcomatous component. The latter would be characterized by scattered and loosely clustered neoplastic cells with one or several primitive nuclei, often with prominent nucleoli and scant to moderate volumes of cytoplasm. Although less frequent, metastatic mesenchymal chondrosarcoma may also be morphologically indistinguishable in smears from the PPB. They consist of small primitive malignant cells focally associated with and embedded within a chondroid matrix material. Finally, desmoplastic small round cell tumors of childhood may arise in the pleura. The neoplastic cells might be expected to be somewhat larger than in PPB and have a rounded contour rather than spindled. In some but not all of these entities in the differential diagnosis, immunocytochemical, ultrastructural, and cytogenetic analyses of aspirated material may be especially useful, just as it would be in tissue examined in the histopathology laboratory.