0
ONLINE EXCLUSIVES
Pulmonary, Critical Care, and Sleep Pearls |

A 34-Year-Old Pregnant Woman With Cough, Chest Pain, and a Left Upper Lobe Mass FREE TO VIEW

Sujith V. Cherian, MD; Karunakar Akasapu, MD; Anupam Kumar, MD; Shakuntala H. Mauzo, MD; Meenakshi B. Bhattacharjee, MD
Author and Funding Information

Dr Kumar is currently at the Department of Pulmonary and Critical Care Medicine, Respiratory Institute, Cleveland Clinic (Cleveland, OH).

aDivision of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, The University of Texas Health Science Center at Houston, TX

bDepartment of Pathology and Laboratory Medicine, The University of Texas Health Science Center at Houston, TX

CORRESPONDENCE TO: Sujith V. Cherian, MD, The University of Texas Health Science Center at Houston, 6431 Fannin St, MSB 1.434, Houston, TX 77030


Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2016;150(3):e87-e91. doi:10.1016/j.chest.2016.03.008
Text Size: A A A
Published online

A 34-year-old white woman who was 30 weeks’ pregnant initially presented to her primary care physician with a cough for which she was given antibiotics, but she had persistent symptoms. These were followed by chest pain, as a result of which she was referred to our department. She had a past medical history of hypertension, and currently was in her sixth pregnancy, with no reported complications in the previous pregnancies. Review of systems was otherwise negative. She had a three-pack-year smoking history, but denied smoking during her current pregnancy.

Figures in this Article

Vital signs were BP 108/64 mm Hg, pulse rate 90 beats/min, respiratory rate 20 breaths/min, and oxygen saturation 96% on room air. She was afebrile and was not in any acute respiratory distress. The remainder of her examination was unremarkable except for her gravid uterus on abdominal examination.

Complete blood count and complete metabolic panel were normal. Chest CT scan demonstrated a large left upper lobe mass (7.7 × 6.7 × 8.2 cm) that extended to the left hilum and the left mainstem bronchus, with possible invasion of the chest wall limited to parietal pleura but not the chest wall musculature or ribs (Fig 1). Bronchoscopy demonstrated tumor extending into the left mainstem bronchus (Fig 2). Fine-needle aspiration and endobronchial biopsies were performed. The smears from the biopsies were cellular and composed of epithelial and stromal elements. The polypoid fragments of epithelium had a tubulopapillary pattern with a single layer of bland-appearing, columnar, nonmucinous cells with no cilia or goblet cells, reminiscent of developing lung with a focal squamous morule. Immunohistochemistry revealed the epithelial component of the tumor to be positive for pancytokeratin, thyroid transcription factor 1 (TTF-1) and β-catenin. Ki-67 was almost 100% in the epithelial component. The stromal component of the tumor had low proliferative activity. The focal squamous morule was positive for chromogranin and synaptophysin (Fig 3).

Figure 1
Figure Jump LinkFigure 1 A, Chest CT mediastinal window showing left upper lobe mass with chest wall involvement and abutting the pulmonary artery trunk. B, Chest CT lung and mediastinal window showing the left upper lobe mas with extension into the left mainstem bronchus. C, Chest CT scan lung window in coronal plane showing left upper lobe mass with left mainstem bronchus involvement.Grahic Jump Location
Figure 2
Figure Jump LinkFigure 2 Bronchoscopic view of the tumor at the level of the left mainstem bronchus.Grahic Jump Location
Figure 3
Figure Jump LinkFigure 3 A, B, Low-power view of endobronchial biopsy (hematoxylin-eosin, original magnification ×40) showing epithelial component resembling developing lung and scant stroma without atypia (A) and squamous morule (B). C, Ki-67 approaching 100% within the epithelial component (original magnification ×100). D, Squamous morule staining positive for synaptophysin (original magnification ×100). E, Epithelial component staining positive for thyroid transcription factor 1 (original magnification ×100). F, Epithelial component staining positive for β-catenin (original magnification ×200).Grahic Jump Location

What is the diagnosis?

Diagnosis: Pulmonary blastoma, well-differentiated fetal adenocarcinoma of the lung

Pulmonary blastoma (PB) is a rare sarcomatoid neoplasm of the lung, making up approximately 0.25% to 0.5% of primary lung cancers. The first case described in 1945 was termed “embryoma of the lung” because it resembled fetal lung of gestational age 10 to 12 weeks, and was later categorized as PB in 1961. It is currently subdivided into three categories: well-differentiated fetal adenocarcinoma (WDFA), pleuropulmonary blastoma (PPB), and classic biphasic pulmonary blastoma (CBPB). The term biphasic refers to the dual presence of epithelial and stromal components within the mass of the tumor. WDFA and PPB are classically monophasic tumors with a predominant epithelial component and a mesenchymal component, respectively. According to the 2004 World Health Organization classification, WDFA has been categorized to be a variant of adenocarcinoma.

Knowledge of pulmonary blastomas derives from case reports and case series. More than 80% of the reported cases have had a history of tobacco abuse, which suggests a possible causative role in these tumors. Furthermore, adducts of benzopyrene (a product of tobacco smoke) have been detected in PB. A p53 gene mutation with or without p53 protein production has been linked to both CBPB and WDFA. A female predominance of WDFA has been theorized to be secondary to the influence of estrogen through estrogen receptors in concert with gene activation by β-catenin.

The majority of patients with WDFA and CBPB are adults with an average age of 43 years. A male predominance of 1.5:1 in CBPB and a female predominance of 3:1 in WDFA have been reported in a case series. Approximately 40% of all patients with PB are asymptomatic. Given that WDFA are generally smaller compared with CBPB, with an average size of 5.7 cm, they are more likely to be asymptomatic. Cough, chest pain, hemoptysis, dyspnea, and respiratory distress are commonly described presenting features in different case series. Fever, anorexia, fatigue, multiple chest infections, and pleural effusions have also been rarely reported. PB usually presents as a well-defined lesion on chest radiography, sometimes large enough to opacify the hemithorax, with endobronchial involvement in approximately 25% of the reported cases. They are usually limited to one lung, with an upper lobe predominance reported in some series. Pleural effusion may be present and is more likely to occur in CBPB than in WDFA.

Diagnosis is made with biopsy; however, obtaining a correct diagnosis with bronchoscopy is difficult given the peripheral nature of these tumors, and is possible only in 25% of cases. In the majority of cases described, diagnosis was made by surgical resection. Specimens obtained by bronchoscopy are generally too small to fully characterize the pleomorphic nature of the tumor. The diagnosis of pulmonary blastoma on bronchoscopy should be strongly considered if two different cell lines are present on histologic examination. Histologically, WDFA is composed of neoplastic glands and tubules lined by nonciliated columnar cells with supranuclear and infranuclear vacuoles mimicking secretory endometrial glands, which are rich in glycogen. Differentials to WDFA include CBPB, which is differentiated from WDFA based on sarcomatous or mesenchymal components, other high-grade malignancies such as lung adenocarcinoma of fetal lung type, and clear cell adenocarcinoma with fetal lung features—both of which are heterogeneous with nonfetal-lunglike elements of various growth patterns and occur in elderly men who have been heavy smokers.

Surgical resection is the treatment of choice for PB. WDFA, in the absence of metastasis, after adequate surgical resection has a much better prognosis than CBPB. Previous studies suggest that the 10-year survival for WDFA is approximately 75%, whereas that for CBPB is approximately 15%. In WDFA, a poor prognosis is associated with thoracic adenopathy, metastases at the time of presentation, and tumor recurrence after surgery. In the presence of these factors, generally the expected survival is 18 to 34 months. Chemotherapy and radiotherapy have been used for advanced tumors in an attempt to downstage the tumor before resection or in inoperable tumors with objective responses. No treatment guidelines have been established for inoperable cases. Chemotherapy regimens are selected arbitrarily and include various combinations of cisplatin, etoposide, ifosfamide, mitomycin C, pemetrexed, and docetaxel with varying success, along with radiotherapy.

Clinical Course

Owing to endobronchial involvement of the tumor, a diagnosis by bronchoscopy and endobronchial biopsy was possible. The presence of the epithelial component resembling developing lung and scant stroma helped clinch the diagnosis of WDFA. The patient in our study was deemed to not be a candidate for surgical intervention, given the extent of the tumor, and was started on chemotherapy with doxorubicin, cisplatin, and etoposide after her pregnancy. However, she failed to respond to this regimen. Other chemotherapy regimens with cisplatin and docetaxel first, followed by cisplatin and pemetrexed, with concurrent radiation therapy were also given to which the patient did not respond. She subsequently exhibited skeletal metastatic lesions and succumbed to her illness 2 years after the initial diagnosis.

  • 1.

    Pulmonary blastoma (well-differentiated fetal adenocarcinoma), a variant of adenocarcinoma, is a rare lung malignancy presenting in the third to fourth decade of life and has a predilection to involve the upper lobes.

  • 2.

    Diagnosis often requires surgical resection because bronchoscopy (especially for peripheral lesions) yields a diagnosis in only approximately 25% of cases, as the majority of cases present as a peripheral lung mass and do not have endobronchial involvement.

  • 3.

    Surgical resection is the mainstay of therapy, with a 75% 10-year survival after resection in WDFA. Chemoradiation therapy may be considered in inoperable cases, as neoadjuvant therapy to downsize the tumor size before surgical excision, and in incompletely resected cases.

  • 4.

    Mediastinal adenopathy, metastases at the time of presentation, and tumor recurrence after surgery are poor prognostic factors in patients with pulmonary blastoma. The expected survival in the presence of these factors is approximately 18 to 34 months.

Financial/nonfinancial disclosures: None declared.

Other contributions:CHEST worked with the authors to ensure that the Journal policies on patient consent to report information were met.


Figures

Figure Jump LinkFigure 1 A, Chest CT mediastinal window showing left upper lobe mass with chest wall involvement and abutting the pulmonary artery trunk. B, Chest CT lung and mediastinal window showing the left upper lobe mas with extension into the left mainstem bronchus. C, Chest CT scan lung window in coronal plane showing left upper lobe mass with left mainstem bronchus involvement.Grahic Jump Location
Figure Jump LinkFigure 2 Bronchoscopic view of the tumor at the level of the left mainstem bronchus.Grahic Jump Location
Figure Jump LinkFigure 3 A, B, Low-power view of endobronchial biopsy (hematoxylin-eosin, original magnification ×40) showing epithelial component resembling developing lung and scant stroma without atypia (A) and squamous morule (B). C, Ki-67 approaching 100% within the epithelial component (original magnification ×100). D, Squamous morule staining positive for synaptophysin (original magnification ×100). E, Epithelial component staining positive for thyroid transcription factor 1 (original magnification ×100). F, Epithelial component staining positive for β-catenin (original magnification ×200).Grahic Jump Location

Tables

References

NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Find Similar Articles
CHEST Journal Articles
PubMed Articles
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543