Classical biphasic pulmonary blastoma in a young woman: case report and review of literature

Abstract

Pulmonary blastoma (PB) is a very rare malignant lung tumor, consisting of immature epithelium and/or mesenchymal tissue. The two tissue components are derived from the same precursor cells. In this study, we present a case of a 29-year-old woman with classical biphasic pulmonary blastoma, who underwent right middle lobe resection and subsequent treatment. Due to the low incidence rate and the reclassification of PB, no standard treatment is available currently. In our case, the patient received radiotherapy and chemotherapy and is doing well at 6 months’ follow up. In retrospect, we review the pathology, clinical manifestations, imaging features and treatment of this disease.

Introduction

Primary pulmonary diphasic differentiation tumor is a very rare malignant tumor. Pulmonary blastoma (PB), comprising approximately 0.25%-0.5% of all lung malignancies, is considered to consist of immature epithelium and/or mesenchymal tissue, similar in morphology to fetal lung tissue [1-4]. Since its first description it was called “lung embryoma” [5,6]. Furthermore, there is no standardized treatment for this disease. The prognosis of classic biphasic pulmonary blastoma is poor and the overall 5-year survival rate is around 15% [7,8]. Herein, we describe a 29-year-old woman with classic biphasic pulmonary blastoma (CBPB), who received comprehensive treatment in our unit.

Case report

A 29-year-old woman presented with cough and phlegm accompanied by blood in sputum for three months. On chest X-ray examination at local hospital an abnormal shadow was detected on the right lung field. After 2 weeks of anti-inflammatory treatment, the condition did not alleviate. She was then transferred to our hospital for treatment. Contrast enhanced chest CT was performed which revealed a 5.1×4.1×4.1 cm nidus in the middle lobe of right lung (Figure 1). The boundary of the lesion was clear and smooth, the enhancement was uneven, and many small patches of necrosis could be seen in it. In addition, several large vessels were seen passing through the margin and inside the lesion. Tumor marker examination revealed gastrin-releasing peptide precursor was 116.30 pg/ml, and cytokeratin 19 fragment was 5.88 pg/m. A CT-guided percutaneous needle biopsy of the lung tumor was performed. Results showed that the epithelial cells had adenoid and squamous cell distribution. Immunohistochemical staining showed ER (-), PR (-), TTF-1 (+), P40 (+), and CDX2 (+), mainly composed of adenocarcinoma. Some of the tumor cells expressed P40, suggesting the possibility of adenosquamous carcinoma (Figure 2).

Figure 1.

Typical CT (computed tomography) images of our patient. Contrast enhanced chest CT was performed which revealed a 5.1×4.1×4.1 cm nidus in the middle lobe of right lung. (A) Lung window, (B) Mediastinal window, (C, D) Coronal and sagittal CT.

Figure 2.

The results of CT-guided puncture. (A) Epithelial cells had adenoid and squamous cell distribution, (B) Immunohistochemical staining showed ER (-), PR (-), TTF-1 (+), P40 (+), and CDX2 (+), mainly composed of adenocarcinoma. Some of the tumor cells expressed P40.

With the consent of the family, we performed right middle lobectomy with lymph node dissection under electronic thoracoscopy. Macroscopically, the solid nature of the lesion was soft, and most of the lesions were necrotic and clearly demarcated from the surrounding tissues. No exact involvement was found near the chest wall. A histopathologic examination showed that the tumor cells were adenoid, arranged with squamous differentiation, and heteromorphic spindle cells were seen. Immunohistochemical staining showed CK (epithelial component +), TTF-1 (adenoid region +), CgA (-), P40 (squamous differentiation component +), vimentin (spindle cell +), desmin (-), CD34 (partial spindle cell +), Ki67 (epithelial region 60%, spindle cell region 30%), SMA (-), and beta-catenin (+) (Figure 3). Tumors had dual differentiation, most of which were low-grade fetal adenocarcinomas, and a few (about 3%) were immature mesenchymal cells, which is consistent with pulmonary blastoma. Subsequently, she received radiotherapy and nedaplatin as chemotherapy and is doing well at 6 months’ followup.

Figure 3.

Postoperative pathologic results. A. Tumors show classical biphasic differentiation. B. Immunohistochemical staining showed CK (epithelial component +), TTF-1 (adenoid region +), CgA (-), P40 (squamous differentiation component +), vimentin (spindle cell +), desmin (-), CD34 (partial spindle cell +), Ki67 (epithelial region 60%, spindle cell region 30%), SMA (-), and beta-catenin (+).

Discussion

PB is an uncommon primary lung malignancy with a frequency of only 0.25-0.5% of primary lung malignancies [1-4]. It was first described by Barrett in 1945, and then Barnard named it as “embryoma”. Later it was renamed as “pulmonary blastomalater” [5,6,9]. In the past, PB was classified into three subgroups: (1) classic biphasic pulmonary blastoma (CBPC), characterized by histopathologic heterogeneity, i.e. intermixing of epithelial and mesenchymal malignant cells, (2) well-differentiated fetal adenocarcinoma (WDFA), characterized by a monophasic epithelial tumor, and (3) pleuro-pulmonary blastoma (PPB), characterized by a monophasic mesenchymal tumor. According to the 2015 WHO classification, PB is considered as a type of sarcomatoid carcinoma and is defined as a biphasic tumor consisting of fetal adenocarcinoma (typically low-grade) and primitive mesenchymal stroma [10]. Actual cases of PB may be less than those previously reported because many earlier reports on PB have included fetal adenocarcinoma and PPB [11].

Regarding its prevalence, some studies suggested that the incidence of this disease is higher in males than in females [12]. However, due to the low incidence of this disease, there is no definite statistical difference at present. Although some reports have suggested that smoking is associated with this disease, the etiology of the disease remains uncertain [13-16]. According to the literature, the average age of pulmonary blastoma is 39-40 years old [12,15]. PB has no specific clinical symptoms. Studies have found that about 60% of patients may show chest pain, cough, and hemoptysis, while others are often found by accident [15-17]. In our patient, cough and phlegm accompanied by blood in sputum were the major symptoms.

Currently, there is no specific serum marker for pulmonary blastomas [18]. Serum levels of tumor markers, AFP, NSE, and CEA, were increased in our patient as reported in the previous reports. Especially, increased AFP positive tumor cells have been seen in most pulmonary blastoma cases [19,20]. In this case study, we found abnormal increases in gastrin-releasing peptide precursors and cytokeratin 19 fragments. On imaging, lesions often present as solitary masses in the peripheral pulmonary zone with clear margins. Contrast enhanced CT scans often show a heterogeneous enhancing soft tissue mass with smooth or lobulated margins and probable areas of necrosis [21]. In this patient, in addition to the above findings, several large blood vessels were seen passing through the lesion and surrounding the lesion.

Due to the biphasic differentiation of tumors, general fine needle aspiration biopsy often cannot make a definite diagnosis due to lack of materials. The diagnosis depends on postoperative pathologic analysis [11,15]. Immunohistochemical analysis is of great significance in the diagnosis of this disease, especially combining epithelial markers with mesenchymal markers [22-24]. Similar to previous literature, we found CK (epithelial component +), TTF-1 (adenoid region +), P40 (squamous differentiation component +), vimentin (spindle cell +), CD34 (partial spindle cell +), Ki67 (epithelial region 60%, spindle cell region 30%), and beta-catenin (+) on immunohistochemical examination. Tumors have dual differentiation, most of which are low-grade fetal adenocarcinomas, and a few (about 3%) are immature mesenchymal cells.

Until now, there has been no standard management of this malignant tumor. Surgical resection, including lobectomy and pneumonectomy, is considered the primary treatment for PB. The role of adjuvant therapy has not been well consolidated because it is still rare, though radiotherapy and chemotherapy regimens are progressing rapidly [25]. The prognosis of biphasic pulmonary blastoma is extremely poor as distant metastasis is common. As reported, the 5-year survival rate and 10-year survival rate of BPB are 16%-25% and 8% respectively [13]. The reported median survival is 26 months in patients undergoing lobectomy or lobectomy, and the median survival is 9 months in patients undergoing pneumonectomy [26]. In our case, the patient underwent a right middle lobe resection and was treated with nedaplatin. After a follow-up of six months, the patient’s condition was stable and no recurrence or distant metastasis was observed.

Conclusions

Classical biphasic pulmonary blastoma is rare. Surgical resection is the main method for its treatment. In addition, radiotherapy and chemotherapy have also been reported, but so far, no consensus has been reached.

Disclosure of conflict of interest

None.