CASE REPORT

A RECURRENCE BIPHASIC PULMONARY BLASTOMAAFTER ADJUVANT CHEMOTHERAPY: A CASE

REPORT OF RARE LUNG MALIGNANCYAsmaa Lakhdissi∗, Ibrahim Elghissassi∗, Khadija Bellahammou∗, Salif Balde∗, Sarra Akla∗, Mustapha Azakhman∗∗, Fouad

Zouaidia∗∗, Najat Mahassini∗∗, Fadoua Rais4, Nourredine Benjaafer4, Hind Mrabti∗, Hassan Errihani∗, Mila Kayryakova♦ andIvan Inkov♦

∗Department of Medical Oncology, National Institute of Oncology, Rabat, Morocco., ∗∗Department of Pathology, Ibn Sina Hospital, Rabat, Morocco.,4Department of Radiotherapy, National Institute of Oncology, Rabat, Morocco., ♦Department of Thoracic Surgery, MMA Sofia, Sofia, Bulgaria.

ABSTRACTPulmonary Blastoma is a rare malignant lung tumour. The Biphasic pulmonary blastoma is composed of a mixture ofimmature epithelial and mesenchymal tissue resembling fetal lung tissue with poor prognosis. Surgery is the treatment ofchoice. The strategy of treatment remains unclear due to the infrequency of this tumour. We report a case of 26-years-oldwoman presenting biphasic pulmonary blastoma. The patient was treated with surgery and six cycles of adjuvantchemotherapy Etoposide-Cisplatin. Before undergoing adjuvant radiotherapy due to positive margins, she developeddyspnea, and the CT scan showed a massive local recurrence tumour compressing the heart. The patient received apalliative radiotherapy in the chest at a dose of 20Gy followed by palliative chemotherapy based on Adriamycin andIfosfamide. The assessment will be programmed after three cycles.

KEYWORDS: Biphasic pulmonary blastoma, chemotherapy, Radiotherapy.

Introduction

The pulmonary blastoma is a rare primary lung tumour thataccounts for 0.25 to 0.5% of pulmonary malignancies [1].It isderived from fetal lung tissue. The biphasic pulmonary blas-toma is composed of a mixture of epithelial and mesenchymaltissues. This tumour type is usually present in male adults andis common among smokers [1]. Surgery is the mainstay treat-ment. However, literature regarding the efficacy of adjuvant

1Department of Medical Oncology, National Institute of Oncology, Rabat, Morocco.Email: asmaalakhdissi@gmail.com

chemotherapy and radiotherapy is poor, and the adjuvant treat-ment should be considered for some patients. The spread of thisaggressive malignancy can be local or distant. Furthermore, theprognosis of this tumour is poor.

We report a case of biphasic pulmonary blastoma with re-currence after surgery and adjuvant chemotherapy. Also, theirclinical, pathological and treatment variability are reviewed.

Case report

We present a case of 26-years-old woman with an unremarkablepast medical history. She was admitted to the National InstituteOf Oncology in Rabat, Morocco for persistent left chest pain,dyspnea, severe productive cough and lost weight. There wasno history of fever or night sweats.

Physical examination revealed reduced breath sounds andsensibility at the palpation of the left hemithorax.

The chest X-ray showed a large opacity in the left hemitho-rax [Figure 1]. The computed tomography scan showed a largeheterogeneous mass measuring 13x17 cm located in the lefthemithorax with central hypodensity.This mass was responsible

Copyright © 2017 by the Bulgarian Association of Young SurgeonsDOI:10.5455/ijsm.pulmonary-blastoma-recurrenceFirst Received: August 15, 2017Accepted: September 06, 2017Manuscript Associate Editor: George Baitchev (BG)Editor-in Chief: Ivan Inkov (BG)Reviewers: Drazen Servis (DE); Cem Onal (TR)

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Fig. 1. Chest X-ray showed a gross opacity in the left hemithorax.

Fig. 2. Chest CT scan showed abnormal mass located in the lefthemithorax with central hypodensity.

Fig. 3. The morular structures of the epithelial tissue inside themalignant mesenchymal stroma.

Fig. 4. The malignant mesenchymal tissue.

Fig. 5. CT scan showed a large heterogeneously mass mea-suring located in the left hemithorax with central hypodensitycompressing the heart and associated to left pleural and peri-cardic effusion.

for the mediastinal shift to the right, atelectasis of the lowerlobe and pleural effusion. Moreover, no nodular lesions or hilarlymphadenopathy were observed.[Figure 2] Also, a scan guidedbiopsy of a tumour was performed. Pathology of the tissueshowed necrotic material with no malignant cells. The patientunderwent a surgical removal of a tumour. The resected tumourweighed 1kg 400 grams and measured 26x15cm with necroticand hemorrhagic rearrangements. The microscopic examinationof the tumour demonstrated mixed epithelial and mesenchymalmalignancies. On the one hand, the epithelial tissue was com-posed of atypical epithelial cells with basophil nuclei and moru-lar structures. On the contrary, The mesenchymal stroma wascomposed of fusiform cells displaying hyperchromatic nucleiand visible variable and also of cystic rearrangements. [Figure 3,4]. It is worth mentioning that the surgical margins were tumoral.The morphological analysis allowed to retain the diagnosis ofbiphasic pulmonary blastoma without recourse to the additionalimmunohistochemical technique. Also, the postoperatively CTscan of chest and abdomen and bone scintigraphy showed nolocal recurrence or distant metastasis.

The patient was referred to the thoracic surgical department

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for a possible intervention due to the positive margins, but nosurgery was possible. Due to the presence of certain poor prog-nostic factors such as biphasic type and size of a tumour higherthan 5cm, an adjuvant chemotherapy was performed includingEtoposide and Cisplatin and was completed after by radiother-apy due to the positive margins.

The patient received six cycles of Etoposide-Cisplatin (Etopo-side 100mg/m2 from day 1 to day 3, cisplatin 80mg/m2 on day1, every three weeks) with safety. Also, before she underwentthe Adjuvant Radiotherapy, the tumour assessment revealeda local recurrence with a large heterogeneous mass measuring15x12x9.7cm located in the left hemithorax with central hypo-density compressing the heart, a left pleural and pericardialeffusion and nodular lesions. [Figure 5].

Our patient underwent palliative radiotherapy at the doseof 20Gy (10x2Gy) and the first cycle of palliative chemotherapybased on Adriamycin and Ifosfamide ( Adriamycin 60mg/m2day 1, Ifosfamide 1.8g/m2 from day 1 to day 5, MESNA 1.8g/m2day 1 to day 5, every 3 weeks with prophylactic granulocytecolony-stimulating factor (G-CSF) day 7 to day 11 and the as-sessment will be programmed after 3 cycles.

Discussion

Pulmonary blastoma is a rare intrathoracic tumour with a fre-quency of 0.25 to 0.5% [1] of pulmonary malignancies. It wasdescribed by Barnard in 1952 as lung embryoma based on thehistological resemblance of a tumour to the fetal lung tissue [2].It is often difficult to diagnose and usually found in the periph-ery of the lung. In 1961, the term of Blastoma was introduced bySpencer [2].Over 200 cases had been reported with distinctivebiological behaviour since the first decription [3] by Barett in1945.

The Pulmonary Blastoma is classified into three subtypes:The first one is biphasic pulmonary blastoma (BPB) with bothepithelial and mesenchymal malignant components. The secondone is well-differentiated fetal adenocarcinoma (WDFA) charac-terised by malignant epithelial component only. The third oneis pleuropulmonary blastoma (PPB) that is a childhood tumourshowing a mesenchymal malignant component only [4]. Ac-cording to the 1999 and 2004 classifications of the World HealthOrganization (WHO), WDFA and PPB are categorised as a vari-ant of adenocarcinoma and soft tissue sarcoma of the lung.[5,6]

The biphasic pulmonary blastoma is the most common of thethree subtypes.[4] It is more frequent in adults and males. It canoccur at any age between birth and seventy years old, and thereis a correlation between smoking and pulmonary blastoma [7].Our patient was a non-smoker female.

A tumour presents with a variety of symptoms includingpain, dyspnea, hemoptysis, and cough. However, approximately40% of cases are asymptomatic [8] with the tumours being foundincidentally on chest X- rays. The radiographic appearanceshows a well-demarcated peripheral or midlung mass with nodefinite lobar predominance [7]. The size of the mass varies froma small peripheral nodule to a mass occupying the entire lobe orhemithorax[9] with the mean tumour diameter is known to be101mm [20-270mm] [4]. For our patient, the mass occupied theleft hemithorax, and the diameter was 170mm at diagnosis.

Because it is hard to obtain tissues containing both an epithe-lial and mesenchymal tumour by biopsy, pathological diagnosisis made by tissues obtained by surgical resection in most casesof pulmonary blastoma. In the present case, the scan guidedbiopsy showed necrotic material with non-malignant cells, and

the diagnosis of Biphasic pulmonary blastoma was made aftersurgical resection.

The surgical excision is the treatment of choice [8,10].Theprognosis is poor with a five-year survival rate of approximately16% [11].The factors that indicate poor prognosis are tumourrecurrence, metastasis at initial presentation, tumour size higherthan 5 cm and lymph node involvement [2,4] The role of adju-vant chemotherapy and radiotherapy is still controversial be-cause of the rarity of this tumour and lack of data.

In our case, the decision to start adjuvant treatment wasbased on the presence of three significant prognostics factorsnamely, the large size of the tumour on presentation (around17cm); biphasic pulmonary blastoma and the positive mar-gins. Data have been extrapolated from experience in treatingprimary pulmonary blastoma in children, which have shownvarying responses to chemotherapeutic agents (cisplatin, cy-clophosphamide, etoposide, vincristine, actinomycin D andAdriamycin)[12].Various combinations of chemotherapeuticdrugs have been tried as a neoadjuvant and adjuvant treat-ment.However, several case reports use a platinum-based adju-vant treatment [4,13].

Regarding literature, One case was treated in an adjuvant set-ting with ICE14 (Ifosfamide-carboplatin and etoposide) and thedecision to start adjuvant treatment was based on the presenceof large size and biphasic subtype of the disease and the patientcontinues to be in remission until the last follow-up. Anothercase was treated in an adjuvant setting with radiotherapy andchemotherapy based on cisplatin and Etoposide and until thereporting of the case, the patient is still in remission [15]. Inanother case, the patient did not receive adjuvant therapy aftersurgery for free margins, but two months later he presented apleural and skin recurrence and was treated with four cyclesof CAV (cyclophosphamide, doxorubicin, and vincristine) withpartial response to the treatment.[16]

Our patient received six cycles of Etoposide-Cisplatin, andshe was programmed to receive a radiotherapy due to the posi-tive margins, but the tumour assessment showed a massive localrecurrence.

In advanced disease, there is no standard chemotherapy regi-men. The following regimens provided an objective response:Doxorubicin plus Ifosfamide, CCNU, Cyclophosphamide, Vin-cristine, Etoposide [17].

The radiotherapy is reserved for incomplete resections andsymptom palliation. Our patient received a palliative radio-therapy in the chest due to the compressing of the heart, andnow she starts a palliative chemotherapy with Adriamycin plusIfosfamide and the assessment will be programmed after threecycles.

The main difference between our case and the previously re-ported cases is that our patient received adjuvant chemotherapy,but she presented a massive recurrence immediately after finish-ing the cycles of chemotherapy and before starting the adjuvantradiotherapy which illustrates the aggressive of this disease.

Conclusion

An adult Biphasic pulmonary blastoma is a sporadic lung tu-mour present as a large invasive mass. The diagnosis and treat-ment have to be planned by a multidisciplinary team. Due to therarity of a tumour and the lack of data, the strategy of treatmentremains unclear. We need a prospective database to identifythe role of adjuvant chemotherapy and radiotherapy followingsurgery depending on the stage of a tumour, prognostic factors

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and also to better define the most effective regimen in advanceddisease.

Authors’ Statements

Competing InterestsThere were no financial support or relationships between the

authors and any organization or professional bodies that couldpose any conflict of interests.

CONSENT STATEMENT

Written informed consent was obtained from the patient‘s nextof kin for publication of this case report and any accompanyingimages. A copy of the written consent is available for review bythe Editor-in-Chief of this journal.

STATEMENT OF ETHICAL APPROVAL

The medical staff of the centre decided patient’s treatment; oralconsent was obtained from all the patients and was approvedby the institutional review boards of the National Institute ofOncology, Cancer Centre in Rabat.

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