Biphasic pulmonary blastoma: An unusual presentation with chest wall, rib, and pleural involvement.

Sir,

Pulmonary blastoma is a rare malignant tumor of uncertain histogenesis with distinctive pathological features, clinical course, and prognosis. It is a very rare malignant neoplasm of the lung that represent 0.25-0.5% of all lung tumors and resembles fetal lung of gestational age of 10-12 weeks.[1] Biphasic pulmonary blastoma (BPB) is a subgroup of pulmonary blastoma that has characteristic histological heterogeneity with an epithelial component, similar to that seen in fetal adenocarcinoma, and a primitive mesenchymal stroma that may contain malignant heterologous elements.[2]

Classical BPB usually presents with nonspecific respiratory symptoms such as cough, hemoptysis, dyspnea, and chest pain. About 40% of cases are asymptomatic and found coincidentally. The usual radiological appearance consists of a well-circumscribed mass measuring 2.5-25 cm in diameter.[3] Pleural effusion occurs very occasionally and chest wall with rib involvement in adult BPB is probably not reported previously. Present report describes a case of classical BPB in a 68-year-old male patient presenting with a huge mass at left lung involving the pleura, rib, and chest wall in view of its rare occurrence and unusual presentation. The literature of this tumor is also briefly reviewed with recent insights into the origin of this tumor.

A 68-year-old smoker male, farmer by occupation presented with history of dry cough and left-sided chest pain for last 6 months. The pain was dull aching and partly relieved by analgesics. He had one episode of scanty hemoptysis about 15 days back. He denied any history of fever, expectoration, or breathlessness. He was receiving unsupervised antituberculosis therapy for last 4 months but without any response. His past medical history was otherwise negative.

On physical examination, he was well built with slight pallor and clubbing but without any lymphadenopathy. Respiratory system examination revealed a grossly deformed chest with an obvious fullness rather a bulging mass at left chest wall in axillary area with slight flattening at the mammary region. Localized tenderness was also evident at and around the abnormally bulging area on left sided chest wall. The right side chest was normal. There was diffuse dull percussion note and decreased pneumophonation all over at left lung fields. Other body system examination was unremarkable.

His investigation revealed normal blood count and blood biochemistry. Induced sputum was negative for acid-fast bacilli. Chest radiography revealed a diffuse homogenous opacity occupying almost whole of left lung field. His electrocardiogram (ECG) and ultrasound abdomen was reported as normal. Computed tomography (CT) scan thorax revealed a giant malignant mass in and around left main bronchus with its complete obliteration and also infiltrating the left upper lobe and lingula. Large necrotic areas were also seen within the mass with its clear demarcation from solid areas on contrast administration. Left side chest wall was also invaded by the lesion with destruction of upper left sided ribs. The mass was bulging through the chest wall laterally. The left lower lobe was compressed with partial aeration and infiltration of the superior and anterior segment. Moderate pleural effusion and mediastinal invasion was also evident on left side [Figure 1]. In view of a possible neoplastic lesion on clinical and radiological assessment, a fine needle aspiration cytology (FNAC) of the lesion was performed that revealed mostly inflammatory cells with few atypical cells. For definitive diagnosis, multiple trucut lung biopsies were done that on histological examination revealed classical malignant biphasic growth pattern with well-defined tubular structures lined by single or more layers of hyperchromatic cells (epithelial component) surrounded by undifferentiated mesenchymal tissue consisting of oval-to-spindle shaped cells with hyperchromatic nuclei (mesenchymal component). These features were consistent with the diagnosis of classical BPB [Figure 2]. On immunohistochemistry, the glandular component was positive for cytokeratin and epithelial membrane antigen (EMA), while the pleomorphic stromal component was positive for vimentin and smooth muscle antigen (SMA).

Figure 1

Computed tomography (CT) scan chest showing a large heterogeneous mass occupying left lung with involvement of ribs, chest wall, and pleural effusion

Figure 2

Photomicrograph of tumor biopsy showing oval-to-spindle shaped cells with hyperchromatic nuclei (representing mesenchymal component) and tubular structures lined by single and multiple layers of hyperchromatic cells (representing epithelial component) (H and E, ×400)

In view of extensive local spread and poor performance status, surgery was not possible, hence radiotherapy was offered to the patient with palliative supportive care. Patient survived 1 month after the tissue diagnosis.

Pulmonary blastoma is a rare tumor with distinctive biological behavior. In 1952, it was first described by Barnard[4] as an ‘embryoma’ in a case where the initial provisional diagnosis was hydatid cyst. Subsequently in 1961, Spencer[5] coined the term ‘pulmonary blastoma’ for this entity in view of its resemblance with fetal tissue. Koss et al.,[6] further subdivided this entity into three categories based on tissue component: (i) Monophasic pulmonary blastoma, known as the well-differentiated fetal adenocarcinoma (WDFA) having epithelial malignant component only; (ii) the classic BPB characterized by both epithelial and mesenchymal malignant components; and (iii) pleuropulmonary blastoma (PPB), that is a childhood tumor with features of mesenchymal malignant components only and currently regarded as a separate entity. Under the 2004 World Health Organization (WHO) classification of lung tumors, pulmonary blastoma is a subtype of sarcomatoid non-small cell lung carcinoma (NSCLC).[7] Classical BPB is the most common of these three subtypes.

Classical BPB is more frequent in 4th decade with a slight male preponderance. The affected individuals usually have tobacco smoking background. Common presenting symptoms are cough, chest pain, hemoptysis, and dyspnea; however, up to 40% of patients may be asymptomatic. Pleural effusion may be present but it is not a predominant abnormality.[8] To the best of our knowledge chest wall, rib, and pleural involvement simultaneously at the time of presentation has not been reported previously as seen in our case.

Radiologically, BPB usually presents as a solitary, well-defined, peripheral lesion. On CT thorax, the lesion often shows solid components with necrotic areas as seen in our case. The size of the lesion may be variable, with a reported average size of about 10 cm. Few CT reports have described a low attenuation mass with ‘whorls’ of solid tissue within the lesion, however this is not a universal findings.[9] Preoperative diagnosis is usually difficult because chest radiograph, sputum cytology and bronchoscopy are usually unrewarding.[10] In most of the published cases, the diagnosis was postoperative following the surgical resection. Similar to the present case, recently there are also reports of having a firm tissue diagnosis preoperatively by percutaneous transthoracic lung biopsy due to adequate tissue sampling.[11]

The histogenesis of this tumor is largely disputed. It has been termed as embryoma, blastoma, and carcinosarcoma; with the blastoma being the most commonly used term. It is exactly not known whether the tumor arises only from the endoderm or endoderm and mesoderm. It is also not clear whether; rather benign looking blastoma and frank carcinosarcoma really belong to one group as two ends of spectrum or represent entirely different lesion.[10] Molecular diagnostic studies have resolved some controversial theories regarding the pathogenesis of BPBs in recent years. Immunohistochemical studies show that the epithelial markers are confined to the tubular element of the tumors, while mesenchymal markers are confined to the stromal element. However, c-kit is strongly expressed in both the components of a tumor, supporting the origin of the BPB from a single pluripotent cell. Whole genome allelic imbalance studies also suggest the monoclonal origin of this biphasic tumor and the heterogeneity seen within the tumor due to differences in the accumulated genetic alterations in each component. Common mutations found in biphasic blastomas are p53 and β-catenin while kras mutations are rare.[12] Strong cytoplasmic expression of CD117 in both mesenchymal and epithelial cells also suggests a single origin and supports the idea that BPB arises from a pluripotential cell that can differentiate into both stromal and epithelial morphologies.[13]

Surgical resection is the treatment of choice. The role of adjuvant chemotherapy and radiotherapy is not yet established. Frankly there are no recommended guidelines for management of this tumor. The prognosis is usually poor and about two-thirds of patients die within 2 years of diagnosis. The adverse prognostic indicators are tumor size more than 5 cm, metastatic disease at initial presentation, tumor recurrence, etc.[6]