Cytologic features of pulmonary blastoma.

Pulmonary blastomas are rare lung neoplasms constituting 0.5% of all lung tumors. This tumor has an aggressive course and needs to be recognized on cytology. A preoperative diagnosis of pulmonary blastoma is difficult to obtain by cytopathologic methods. A diagnosis of biphasic pulmonary blastoma should be considered when there is a dimorphic population of cells on cytology. A 30-year-old male presented with gradually progressing breathlessness and left-sided chest pain for the past one month. Chest radiograph and computed tomography of thorax revealed an anterior mediastinal mass that was subjected to ultrasound-guided fine-needle aspiration cytology. Aspiration cytology showed a highly cellular lesion with a dimorphic population of tumor cells in a necrotic background. The possibility of a non-small cell carcinoma was suggested. Subsequent histopathology revealed the tumor to be a pulmonary blastoma. The importance of recognizing the dimorphic population of cells in cytology is discussed.

Introduction

Pulmonary blastoma is a rare lung neoplasm constituting 0.5% of all lung cancers, with a histological resemblance to fetal lung tissue. Classic biphasic pulmonary blastoma (CBPB) is a subgroup of pulmonary blastoma characterized by a unique histological heterogeneity with intermixing of both epithelial and mesenchymal malignant components. The tumor progresses rapidly and therefore prognosis is very poor.[1] Although well described histologically, it is scarcely mentioned in the cytology literature. We report a case of CBPB and discuss the role of cytology in the diagnosis of this relatively rare neoplasm.

Case Report

A 30-year-old, non-smoker and previously healthy male presented with gradually progressing breathlessness and left-sided chest pain for the past one month. Chest radiograph revealed left-sided pleural effusion. The hemorrhagic pleural fluid sent for cytological evaluation showed pleomorphic malignant cells. Computed tomography (CT) of thorax revealed a heterogeneously enhancing lesion in the left hemithorax, with a major portion in anterior mediastinum with left hilar involvement. Ultrasound-guided fine needle aspiration cytology (FNAC) was performed from the anterior mediastinal mass and smears were stained with hematoxylin and eosin (H and E) and May-Grünwald Giemsa stain (MGG).

Smears were highly cellular showing dimorphic pattern [Figure 1]. One cell type was predominantly ovoid-to-elongated with spindle-shaped nuclei, coarse chromatin and scant cytoplasm. The other cell type was round-to-polygonal with finely vacuolated cytoplasm. The nuclei were hyperchromatic with indistinct nucleoli [Figure 2]. The final cytological diagnosis was given as non-small cell carcinoma probably from lung. Subsequently the patient underwent CT-guided biopsy.

Figure 1

Cellular smears showing two types of malignant cells (MGG, ×100)

Figure 2

Tumor cells with pleomorphic nuclei and indistinct nucleoli (MGG, ×200)

Histopathological examination showed a tumor composed of primitive glandular structures lined by columnar cells with clear and vacuolated cytoplasm surrounded by spindle cell component showing oval plump nuclei [Figure 3]. The nuclei of both components were hyperchromatic and pleomorphic. Foci of blastema components were also seen. Occasional mitotic figures were noted in the spindle cell component. A final diagnosis of classic biphasic pulmonary blastoma was given. Secondary deposits in the lumbar vertebrae with involvement of L2–L3 roots were seen on magnetic resonance imaging. He underwent three cycles of chemotherapy.

Figure 3

Tumor composed of primitive glandular structures lined by columnar cells (H and E, ×200)

Discussion

Pulmonary blastoma is a rare tumor, which was originally termed ‘embryoma’ by Barnard[2] in 1952. The term ‘blastoma’ was introduced in 1961 by Spencer[3] to reflect that the tumor arises from pulmonary blastema in a manner similar to other tumors developing from fetal tissues. Subsequently, pulmonary blastoma have been further subdivided by Koss et al.,[4] into three categories: Classic biphasic pulmonary blastoma (CBPB), well-differentiated fetal adenocarcinoma (WDFA) and pleuropulmonary blastoma (PPB) of childhood.

Well-differentiated fetal adenocarcinoma usually affects middle-aged adults, often with a tobacco smoking history, and has a pathogenesis similar to that of bronchogenic carcinoma. Prognosis is usually better than bronchogenic carcinoma. Pleuropulmonary blastoma are rare intrathoracic tumors, occurring predominantly in children of less than three years of age. Classic biphasic pulmonary blastoma occurs in adults (80%) with a slight male predominance. In adults there is an association with cigarette smoking and in children CBPB has been seen in association with pre-existing benign cysts of the lung.[5] A p53 gene mutation with or without P53 protein overproduction has been linked to both CBPB and WDFA.[6] In general, CBPB presents with nonspecific respiratory symptoms that might mimic a respiratory tract infection with cough, hemoptysis, dyspnea and chest pain. In 40% of the cases, patients are asymptomatic and the lesion was found coincidentally on chest radiographs performed for the other indications. The chest radiographic appearance usually consists of a well-circumscribed mass ranging in size from 1.5 to 13 cm in diameter. On ultrasound, CBPB presents as an echogenic or mixed echogenic mass with cystic areas.[7] This is comparable with the CT appearance of a partly solid and cystic lesion with a necrotic center. The presence of pleural or mediastinal involvement is an indication of metastatic disease.

Classic biphasic pulmonary blastoma is an aggressive tumor associated with a poor prognosis. Surgery is the preferred treatment often with postoperative adjuvant chemotherapy and/or radiotherapy. Prognosis is worse if the tumor is larger than five cm at presentation. Distant metastases are commonly seen.[8] Based on the survey of published cases, the prognosis of patients with CBPB has been as poor as that of patients with common lung carcinomas.

A preoperative diagnosis of pulmonary blastoma is difficult to obtain by cytopathologic methods. A diagnosis of CBPB should be considered whenever epithelial cells and a separate population of stromal cells are seen in a guided FNAC from a pulmonary/mediastinal mass. In addition to the dimorphic population of cells, the presence of cells with vacuolated cytoplasm and the background tigroid effect (because of ruptured vacuolated cells) should cytologically raise the possible diagnosis of a CBPB.

The differential diagnosis in cytologic preparations include other tumors in the small round cell category when only the blastema component is seen in smears. Primitive neuroectodermal tumor arising within thoracic soft tissue is another important differential diagnosis.

The small primitive neoplastic cells from the two may be indistinguishable in smears. Rosette-like structures may be associated with primitive neuroectodermal tumor, which may also show fibrillar background material.

Metastatic tumors to the lung and pleura also need to be considered. Foremost among these would be metastatic neuroblastoma and embryonal rhabdomyosarcoma.

A diagnosis of teratoma should also be entertained when more than one type of cell is seen especially from a mediastinal lesion.

This case is reported to focus on the importance of recognizing the dimorphic cell pattern in cytology smears and to include CBPB in the differential diagnosis.