Rare disease
CASE REPORT
Radical surgical resection for giant primary mediastinal endodermal sinus tumour with pulmonary metastasis after chemotherapy: can be curative Ikram Ulhaq Chaudhry,1 Mohammed Rahhal,2 Imtiaz Khurshid,2 Hadi Mutairi3 1
Department of Chest Surgery, King Fahad Specialist Hospital, Dammam, Saudi Arabia 2 Department of Adult Oncology, King Fahad Specialist Hospital, Dammam, Saudi Arabia 3 Department of Chest Surgery, King Fahad Specialist Hospital, Dammam, Saudi Arabia Correspondence to Ikram Ulhaq Chaudhry,
[email protected] Accepted 25 May 2014
SUMMARY Primary non-seminomatous germ cell tumours of anterior mediastinum are uncommon. Endodermal sinus tumour of the anterior mediastinum (yolk sac) is a rare but lethal neoplasm. We present a case of an 18-year-old man who presented with chest pain, cough and haemosputum with markedly raised serum α-fetoprotein (AFP) levels above 112 000 ng/mL. Chest roentgenogram and CT showed a giant anterior mediastinal mass. CT guided biopsy revealed a diagnosis of endodermal sinus tumour. After the completion of chemotherapy, extensive surgical resection was carried out along with the right lung metastastectomy. Five years postresection follow-up the patient is disease free with normal serum tumour markers. This is the longest survival ever reported of such tumours with highest AFP level (>112 000 ng/mL) and lung metastasis.
BACKGROUND Common primary germ cell tumours of mediastinum are seminoma, choriocarcinoma, teratoma, embryonic carcinoma and endodermal sinus tumours. They represent 1–4% of all mediastinal neoplasms. Endodermal sinus tumour (yolk sac) which has a unique histopathlogical pattern is an uncommon but highly malignant tumour of the mediastinum. Teilum in 1959 described that endodermal sinus tumours arise from extraembryonic endoderm.1 Most patients are young men. They commonly present with a history of cough, shortness of breath and chest pain. Sometimes with fever, haemoptysis, superior vena
To cite: Chaudhry IU, Rahhal M, Khurshid I, et al. BMJ Case Rep Published online: [ please include Day Month Year] doi:10.1136/ bcr-2014-204662
cava obstruction, night sweats and neck mass. Haematological malignancies associated with these tumors have been reported and the most fatal one is haemophagocytic syndrome.2
CASE PRESENTATION An 18 year-old man presented to us with a 2-month history of cough, shortness of breath and haemosputum. He had no medical problems in the past. Physical examination of the neck, chest and abdomen including testis was normal with no palpable lymphadenopathy. Chest X-ray showed a complete opacification of the left hemithorax (figure 1A). CT scan of the chest, abdomen, pelvis and brain was carried out as a routine investigation which revealed a large anterior mediastinal tumour and four right lung metastasis (figure 2A, B). Testicular ultrasound was normal. Basic blood investigations including complete blood count, renal and liver panel were normal. Serum tumour marker showed significantly high levels of α-fetoprotein (AFP) (112 000 ng/mL) and normal β-human chorion gonadotropin (βHCG) and lactate dehydrogenase (LDH) levels. CT-guided biopsy of the mass revealed a diagnosis of endodermal sinus tumour. A multidisciplinary meeting concluded that after the completion of chemotherapy, CT of the chest and tumour markers should be repeated and in case of residual tumour radical surgical resection should be performed provided tumour marker level lowers close to base line (figure 2C). The patient received four cycles of paclitaxil, etoposide, bleomycin (PEB)
Figure 1 (A) Preoperative chest X-ray showing massive anterior mediastinal mass and (B) postoperative chest X-ray after excision of mediastinal mass.
Chaudhry IU, et al. BMJ Case Rep 2014. doi:10.1136/bcr-2014-204662
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Rare disease Figure 2 (A) Preoperative CT scan of the chest showing giant mediastinal mass. (B) CT of the thorax, lung metastasis; (C) CT of the thorax postchemotherapy residual mass; (D) 5-year postoperative CT of the thorax showing no recurrence.
regime chemotherapy cisplatin 20 mg/m2, etoposide 100 mg/m2 and bleomycine 30 mg/m2. After the completion of chemotherapy granulocyte colony-stimulating factor (GCSF) was given. Postchemotherapy CT of the chest revealed a large anterior mediastinal residual mass and repeat AFP level was 240 ng/mL Therefore we decided to proceed for surgical resection. Median sternotomy approach was used and we found a giant mediastinal mass occupying the anterior mediastinum, left hemithorax and there were four lesions in the right lung. We used a special technique which we have previously described.3 In such cases this technique facilitates the dissection to achieve the complete removal of the mass without spillage of the contents in the surgical field while manipulating the mass during surgery. We placed a purse-string suture in the soft part of the mass and inserted a clamped 32F drain and tightened the purse string suture around it. Approximately 450 mL of turbid fluid and necrotic tissues were sucked out. Mass was dissected free of innominate vein, It was densly attached to the pericardium over the ascending aorta and main pulmonary artery. The tumour was dissected free of the aorta, main pulmonary artery and the left superior pulmonary vein and excised along with part of the pericardium en block (figure 3A). Nodules in the right lung were excised using a surgical stapler. The pericardial defect created by resection did not require reconstruction as there was no danger of cardiac herniation due to its anterior location. Histology reports revealed endodermal sinus tumour (figure 3B).
INVESTIGATIONS Chest X-ray, CT of the chest and tumour marker.
DIFFERENTIAL DIAGNOSIS Lung metastasis.
TREATMENT Surgical resection.
OUTCOME AND FOLLOW-UP Five-year follow-up, complete recovery with no recurrence.
DISCUSSION Primary mediastinum germ cell tumours are classified as seminomatous and non-seminomatous based on histology. Mediastinum is the most common site of extra-gonadal primary germ cell tumours. Of these, 50–70% harbour the mediastinum and they have bad prognosis as compared to their gonadal counterpart. Most commonly they occur in the gonads (testis and ovaries), and 10–15% of them occur in the extra-gonadal areas.4 Endodermal sinus tumour has been reported in the midline, pineal gland, anterior mediastinum, retroperitonium and presacreal area based on the theory that during embryogenesis germ cells abnormally migrate along the urogenital ridge. Primary mediastinal endodermal sinus tumour is rare and highly malignant due to rapid growth and early metastasis often to lung, brain, liver and bone.5 Despite recent advances in chemotherapy, long-term survival of patients with primary mediastinal endodermal sinus tumour is poor as compared to their gonadal counterpart and carry a grave prognosis.6 A retrospective study7 from MD Anderson centre from 1993 to 1998 reported 20 cases of non-seminomatous germ cell tumours, nine of them were primary mediastinal endodermal sinus tumours. All patients were treated with chemotherapy followed by radical resection for
Figure 3 (A) Resected mediastinal mass; (B) microscopic section showing clusters of highly malignant epithelial cells with hyperchromatic nuclei with several mitotic cells arranged around the capillaries forming Schiller-Duval bodies. Immunohistochemical stain showing α-fetoprotein positive, and CD30 negative.
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Chaudhry IU, et al. BMJ Case Rep 2014. doi:10.1136/bcr-2014-204662
Rare disease residual mass and the overall survival at 2 years was 58%. Moran et al have reported 38 cases of endodermal sinus tumours over a 30-year period. They have noticed that 72% of the patients died at 36 months follow-up. Kesler et al reported, from 1981 to 1998, 40 cases of endodermal sinus tumours with overall survival of 61% after an average follow-up of 48 months. They noticed three variables which affect the long-term survival, (1) AFP level after chemotherapy, (2) residual mass pathological status and (3) pulmonary metastasis.8 Surgical resection following chemotherapy for a residual tumour is very challenging, and demands high surgical skills as tumours commonly have dense fibrotic adhesions to the pericardium, great vessels and neighbouring structures which obscure the normal anatomy rendering the surgical resection very difficult. The most important prognostic factors for long-term survival are normalisation of serum tumour markers after chemotherapy and complete en block resection of the tumour. In conclusion multimodality aggressive approach for primary mediastinal endodermal sinus tumours including adjuvant
modern chemotherapy followed by extensive surgical resection is the optimal treatment, and can lead to long-term survival even though patient had lung metastasis. At 5 years follow-up by serial tumour marker essay, chest X-ray and CT of the chest and abdomen there is no recurrence (figures 1B and 2D). Contributors IC operated on the patient and wrote part of the manuscript. HM operated on the patient and wrote the manuscript. MR reviewed the manuscript and gave the patient chemotherapy. IK helped with writing the manuscript, editing and references. Competing interests None. Patient consent Obtained. Provenance and peer review Not commissioned; externally peer reviewed.
REFERENCES 1
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Learning points ▸ Multimodality approach for primary mediastinal endodermal sinus tumours even with multiple lung metastases can be curative in selected cases. ▸ Neoadjuvant chemotherapy and adjuvant chemotherapy are necessary to decrease the tumour burden. ▸ Negative resection margins have crucial role for better prognosis. ▸ Tumour marker assay is a useful tool to monitor the clinical response.
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Teilmann I, Kassis H, Pietra G. Primary germ cell tumor of the anterior mediastinum with features of endodermal sinus tumor (mesoblastoma vitellinum). Acta Pathol Microbiol Scand 1967;70:267–78. Hartmann JT, Nichols CR, Droz JP, et al. Hematologic disorders associated with primary mediastinal non-seminomatous germ cell tumors. J Natl Cancer Inst 2000;92:54–61. Chaudhry I, Bojal S, Poovathumkadavil A, et al. Role of surgery after chemotherapy in B-cell lymphoma of thymus causing airway compression and right ventricle outflow tract obstruction. Ann Thorac Surg 2011;92:1120–2. Teilum G. Endodermal sinus tumor. In: Special tumors of the ovary and testis and related extragonadal lesions: comparative pathology and histological identification. Copenhagen: Munksgaard, 1971:33–74. Moran CA, Suster S. Primary germ cell tumors of the mediastinum: I. Analysis of 322 cases with special emphasis on teratomatous lesions and a proposal for histopathological classification and clinical staging. Cancer 1997;80:681–90. Porcu P, Bhatia S, Sharma M, et al. Results of treatment after relapse from high dose chemotherapy in germ cell tumors. J Clin Oncol 2000;18:1181–6. Walsh GL, Taylor GD, Nesbitt JC, et al. Intensive chemotherapy and radical resections for primary nonseminomatous mediastinal germ cell tumors. Ann Thorac Surg 2000;69:337–44. Kesler KA, Rieger KM, Ganjoo KN, et al. Primary mediastinal nonseminomatous germ cell tumors: the influence of post chemotherapy pathology on long term survival after surgery. J Thorac Cardiovasc Surg 1999;118:692–701.
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Chaudhry IU, et al. BMJ Case Rep 2014. doi:10.1136/bcr-2014-204662
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