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CASE REPORT Table of Contents  
Ahead of print publication
A curious case of classic biphasic pulmonary blastoma

1 Department of TB and Respiratory Diseases, National Institute of Tuberculosis and Respiratory Diseases, New Delhi, India
2 Department of Pathology, GSVM Medical College, Kanpur, Uttar Pradesh, India

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Date of Submission12-May-2022
Date of Decision01-Jul-2022
Date of Acceptance03-Jul-2022
Date of Web Publication27-Oct-2022


Classic biphasic pulmonary blastoma is an uncommon and highly aggressive primary pulmonary malignancy characteristically arising from fetal lung tissues comprising biphasic histology that is made up of both epithelial and mesenchymal components. We present this rare case in which a young adult presented with chest pain for 3 months and dyspnea for 1 month. Contrast-enhanced computed tomography of the thorax revealed a right-sided homogeneous mass. The diagnosis was confirmed by transthoracic biopsy and histopathological examination. Surgical excision remains the treatment of choice. Recurrence usually occurs within 12 months of surgery, with 5-year survival rates <20%. We report this rare malignancy with a special focus on improving the management of this malignancy.

Keywords: Smoking, histology, ICE protocol, prognosis, pulmonary blastoma

How to cite this URL:
Vinay V, Saini JK, Dinesh Kanna M N, Srivastava A. A curious case of classic biphasic pulmonary blastoma. J Appl Sci Clin Pract [Epub ahead of print] [cited 2023 Mar 29]. Available from: http://www.jascp.org/preprintarticle.asp?id=358988

  Introduction Top

Biphasic pulmonary blastomas (PB) are rare primary lung tumors that make up 0.25%–0.5% of primary lung cancers.[1],[2] First described by Barnett and Barnard in 1945,[3] and nearly 300 cases have been described worldwide. According to the tissue components, PB falls into three categories: (i) monophasic pulmonary blastoma, (ii) Classic biphasic pulmonary blastoma (CBPB), and (iii) pleuropulmonary blastoma, regarded as a distinct entity currently.[4],[5] Due to its rarity, variable histology, rapid progression, and poor prognosis; diagnosis and management are quite challenging. This case is presented with a brief literature review to aid physicians in faster diagnosis and better treatment and to highlight the role of adjuvant chemotherapy in improving the outcome in patients diagnosed with CBPB.

  Case Report Top

A 30-year-old male, a smoker, presented with chest pain for 3 months and dyspnea for 1 month with no history of fever, night sweats, wheeze, or weight loss. His physical examination revealed an afebrile condition, tachypnea (22 breaths/min), and no lymphadenopathy. Respiratory system examination revealed decreased chest expansion and dullness over the right hemithorax. All other systems were unremarkable. Baseline investigations of the patient were insignificant.

Chest X-ray showed a large homogeneous opacity in the right hemithorax [Figure 1]a. Computed tomography (CT) scan chest delineated a large homogeneous mass (19 cm) involving the right middle and lower lobe [Figure 1]b. Ultrasound-guided aspiration of loculated effusion yielded a dry tap and transthoracic biopsy of the mass revealed biphasic morphology comprising irregular glands and mesenchymal components. The glands were lined by low to high columnar, focally stratified cells with hyperchromatic nuclei. The mesenchymal component shows nuclear pleomorphism with hyperchromatic nuclei and scanty cytoplasm [Figure 2]a and [Figure 2]b. On immunohistochemistry, the glandular component displays nuclear immuno-positivity for thyroid transcription factor-1 (TTF-1) and is negative for vimentin and smooth muscle actin (SMA) indicating pulmonary origin [Figure 2]c, while the mesenchymal component is immuno-positive for vimentin and negative for TTF-1 consistent with pulmonary blastoma [Figure 2]d.
Figure 1: (a) Chest radiograph PA view showing homogenous opacity in the right mid and lower zone. (b) Contrast-enhanced computed tomography thorax showing right-sided mass and loculated effusion. PA: Posteroanterior

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Figure 2: Histopathological Examination (a) ×100 and (b) ×400 showing both epithelial and mesenchymal components consistent with pulmonary blastoma. (c) Immunohistochemistry for thyroid transcription factor-1 demonstrating nuclear immunopositivity, (d) Vimentin immunohistochemistry reveals cytoplasmic positivity in the mesenchymal component

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To assess staging and resectability, a whole-body positron emission tomography CT (PET-CT) was done which showed a large Fluorodeoxyglucose (FDG) avid mass measuring 19.4 cm (maximum standard uptake value 12.8) in the right hemithorax with infiltration of the left atrium, esophagus, and right diaphragmatic crus, with a metastatic nodule and loculated effusion in the right upper lobe. The staging was done similar to non small-cell lung cancer (NSCLC) and labeled as Stage III-A (T4N0M0) according to TNM 8th Edition.[6] After a multidisciplinary discussion (MDD) involving a team of pulmonologists and thoracic surgeons, it was decided to initiate neoadjuvant chemotherapy – Ifosfamide, carboplatin, and etoposide [ICE protocol] based on the patient's age, incomplete resection status, and the lack of evidence supporting adjuvant radiotherapy.

Radiological re-evaluation (contrast-enhanced CT [CECT] thorax) after six cycles of chemotherapy revealed a 60% reduction in the tumor size and complete resolution of pleural effusion, as assessed by the radiologist [Figure 3]. The patient's incomplete resection status made him ineligible for surgery. However, he remains to be in partial response status with chemotherapy.
Figure 3: (a) Chest radiograph (b) Computed tomography of the thorax, post six cycles of chemotherapy showing a reduction in the size of mass (partial response)

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  Discussion Top

Adult PB are unusual primary lung malignancies that are not completely understood but appear to be correlated with cigarette smoking and are categorized into either biphasic or epithelial. It is believed that PB arises from pleuropulmonary mesenchyme.[2] With its primitive epithelial and mesenchymal composition, PB is similar to fetal lung tissue and has been linked to p53 gene mutation with or without p53 protein overproduction.[5] Approximately 40% of cases are discovered by incidental imaging, in most cases with no symptoms. Symptomatic cases commonly present with cough, hemoptysis, chest pain, and dyspnea. Only 1 out of 4 cases can be diagnosed with bronchoscopy or biopsy due to its proximity to pleura. Ultrasound/CT-guided transthoracic biopsy is considered a very effective diagnostic tool.[7] The presence of pleural effusion may be more common with CBPB as compared to well differentiated fetal adenocarcinoma. Only in 25% of the cases, endobronchial growth has been seen.[5]

In CBPB, malignant epithelial and stromal cells combine to form a biphasic tumor. A tubular adenocarcinoma with glycogenated cytoplasm is seen in the epithelial component, while the stroma contains loose undifferentiated mesenchyme with variable degrees of nuclear atypia. The epithelial cell component is diffusely positive for cytokeratin 7, cytokeratin pool AE1-AE3, CEA, TTF-1, milk fat globulin, and focally positive for chromogranin A, synaptophysin, and Clara cell antigen.[5] The mesenchymal cells show diffuse immunoreactivity for vimentin and muscle-specific actin and focally for the cytokeratin pool AE1-AE3.[8]

It is staged in the same manner as NSCLC since no separate staging system exists for PB. Distant metastatic spread to the brain, bone, liver, kidney, pancreas, and adrenal glands by hematogenous route has been described in the literature. PET-CT might help to predict operability and relapse after surgical excision. Surgery is curative for localized diseases.[5],[7] The median survival for 17 patients with unresected disease was 2 months, while the median survival for 66 resected cases were 33 months.[4] Larsen et al. reviewed 108 resected cases in which the median survival was 29 months for lobectomy or minor resection and 9 months for pneumonectomy.[9] Removing distant metastases may have a benefit as well.[10]

The use of radiation therapy as a single therapy has been documented to induce an objective response in a few cases.[9],[11] Using a combined chemoradiation strategy, local pain control and palliation of metastasis were achieved in a few cases.[5] Chemotherapy had a mere 16% response rate. ICE protocol comprising ifosfamide, carboplatin, and etoposide was used in combination as effective chemotherapy for pulmonary blastoma. Remission has been noted after six cycles of ICE therapy.[7] An estimated 5-year survival is only 15%–30%, as biphasic PB has a poor prognosis with nearly 2/3 of patients dying within 2 years with a recurrence rate of 43%.[5],[7] Tumor size >5 cm, biphasic type, metastasis at initial presentation, incomplete resection, tumor recurrence, and lymph node involvement are considered as poor prognostic factors.[5]

In this case, immediately after diagnosis and staging, a MDD was held and a chemotherapy regimen consisting of ifosfamide, carboplatin, and etoposide was initiated based on two important prognostic factors, the biphasic pattern and large size of the tumor (>5 cm) and also to attempt downstaging. Adjuvant radiotherapy was not given due to insufficient data and the presence of poor prognostic features. Infiltration of the left atrium, esophagus, and the right diaphragmatic crus in re-evaluation (using CECT thorax) even after administration of six cycles of chemotherapy rendered the patient ineligible for surgery. Despite response to chemotherapy (partial response)until the last follow-up, the patient is advised to seek immediate medical treatment if new symptoms appear.

Key learning points from this case are

  1. CBPB is an unusual and rare malignant lung tumor in adolescents and young adults.
  2. A multimodality approach to diagnosis, treatment, and follow-up is necessary and surgical excision remains curative.
  3. Conventional chemotherapy or the ICE protocol can be considered in cases where the tumor is inoperable and to attempt downstaging, cases involving the surgical borders, and cases with poor prognostic factors.
  4. Prognosis still remains poor despite best management.


The author is immensely grateful to Dr. Prakash Sivaramakrishnan (DTCD; DNB Respiratory medicine; Fellowship in Interventional pulmonology and thoracic oncology [TATA Memorial centre, Mumbai]; DM Pulmonary Medicine Trainee, AIIMS Rishikesh) for his valuable suggestions regarding the management of this case.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal his identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Bisogno G, Brennan B, Orbach D, Stachowicz-Stencel T, Cecchetto G, Indolfi P, et al. Treatment and prognostic factors in pleuropulmonary blastoma: An EXPeRT report. Eur J Cancer 2014;50:178-84.  Back to cited text no. 1
Wang YX, Zhang J, Chu XY, Liu Y, Li F, Wang ZB, et al. Diagnosis and multi-modality treatment of adult pulmonary plastoma: Analysis of 18 cases and review of literature. Asian Pac J Trop Med 2014;7:164-8.  Back to cited text no. 2
Barrett NR, Barnard WG. Some unusual thoracic tumours. Br J Surg 1945;32:447-57.  Back to cited text no. 3
Koss MN, Hochholzer L, O'Leary T. Pulmonary blastomas. Cancer 1991;67:2368-81.  Back to cited text no. 4
Van Loo S, Boeykens E, Stappaerts I, Rutsaert R. Classic biphasic pulmonary blastoma: A case report and review of the literature. Lung Cancer 2011;73:127-32.  Back to cited text no. 5
Goldstraw P, Chansky K, Crowley J, Rami-Porta R, Asamura H, Eberhardt WE, et al. The IASLC lung cancer staging project: Proposals for revision of the TNM stage groupings in the forthcoming (Eighth) edition of the TNM classification for lung cancer. Thorac Oncol 2016;11:39-51.  Back to cited text no. 6
Shadrach BJ, Vedant D, Vishwajeet V, Jain P, Dutt N, Surekha B, et al. Endobronchial pulmonary blastoma – An unusual presentation of a rare lung malignancy and review of literature. Monaldi Arch Chest Dis 2020;90:528-32.  Back to cited text no. 7
Nakatani Y, Miyagi Y, Takemura T, Oka T, Yokoi T, Takagi M, et al. Aberrant nuclear/cytoplasmic localization and gene mutation of beta-catenin in classic pulmonary blastoma: Beta-catenin immunostaining is useful for distinguishing between classic pulmonary blastoma and a blastomatoid variant of carcinosarcoma. Am J Surg Pathol 2004;28:921-7.  Back to cited text no. 8
Larsen H, Sørensen JB. Pulmonary blastoma: A review with special emphasis on prognosis and treatment. Cancer Treat Rev 1996;22:145-60.  Back to cited text no. 9
Kouvaris JR, Gogou PV, Papacharalampous XN, Kostara HJ, Balafouta MJ, Vlahos LJ. Solitary brain metastasis from classic biphasic pulmonary blastoma: A case report and review of the literature. Onkologie 2006;29:568-70.  Back to cited text no. 10
Surmont VF, van Klaveren RJ, Nowak PJ, Zondervan PE, Hoogsteden HC, van Meerbeeck JP. Unexpected response of a pulmonary blastoma on radiotherapy: A case report and review of the literature. Lung Cancer 2002;36:207-11.  Back to cited text no. 11

Correspondence Address:
Jitendra Kumar Saini,
Head, Department of Thoracic Oncology, National Institute of Tuberculosis and Respiratory Diseases (NITRD), Sri Aurobindo Marg (Near Qutub Minar), New Delhi - 110 030
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jascp.jascp_26_22


  [Figure 1], [Figure 2], [Figure 3]


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