Testicular Mixed Germ Cell Tumor Metastasizing to Heart

R Avasthi*, SC Chaudhary**, D Mohanty**, Kiran Mishra+

*Professor, **Senior Resident, Department of Medicine; +Professor, Department of Pathology; University College of Medical Sciences and GTB Hospital, Delhi-95. Received : 27.12.2007; Revised : 30.6.2008;
Re-Revised : 18.8.2008; Accepted : 4.9.2008

Abstract

A 21 years old male presented with low grade fever, hemoptysis and progressively increasing dyspnoea of four month duration followed by acutely developing dizziness, hypotension, convulsion and altered sensorium. He had been operated (left inguinal orchidectomy) for left testicular swelling two years back with high α-fetoprotein and normal β-human chorionic gonadotropin (β-hCG). In view of this a possibility of metastasis secondary to a malignant testicular tumor was considered. Echocardiography demonstrated a large intracardiac mass, chest computed tomography (CT) revealed intracardiac mass, mediastinal masses and left sided pleural effusion. The histopathology revealed testicular mixed germ cell tumor (MGCT). This case is presented to demonstrate uncommon cardiac manifestations of secondary spread of testicular malignancy. ©

Introduction

Mixed germ cell tumors (MGCTs) are the second most common testicular germ cell tumors, accounting for 40-50% of all primary germ cell tumors. It contain more than one germ cell tumor component in various combinations. The most common combinations are embryonal carcinoma and teratoma (26%), embryonal carcinoma and seminoma (16%) and embryonal carcinoma, yolk sac tumor and teratoma (11%). Pre-pubertal patients rarely have MGCT.1 They usually present with slowly progressive testicular enlargement with or without pain. However, in approximately 10% of patients, the presenting manifestation may be due to metastasis. Common sites of metastases include retroperitoneum, posterior mediastinum, supraclavicular lymph node and pulmonary nodule. Pulmonary metastases are the most common site of visceral organ metastases. Liver, bone, and brain metastasis are less common.2 Metastasis to heart is rarely reported.3 We hereby report a case of non-seminomatous malignant mixed germ cell tumor who presented with widespread metastases to heart, pleura, lungs and mediastinum.

Case Report

A 21-years-old male had been operated (left inguinal orchidectomy) for left testicular swelling two years back. Contrast enhanced computed tomography (CECT) abdomen done at that time was suggestive of large left testicular mass with heterogenous enhancement pattern, without any definite intra-abdominal mass or significant retroperitoneal lymphadenopathy. Alpha-fetoprotein was 6156.88 ng/ml and β-hCG was normal. Histopathological report of testicular mass revealed that tumor is encapsulated by fibrous capsule, composed of a variety of structures of ectodermal, mesenchymal and endodermal origin, arranged in disorderly fashion. Small cystic areas lined by stratified squamous epithelial cells and filled with mucin were seen. Primitive cartilage tissue and fibrocollagenous tissue were also seen. The tissues were cytologically benign and mitotic figures were scarce. Tumor was limited by fibrous capsule and no infiltration into adjacent structures was seen. Impression of testicular teratoma with mature and immature elements was made by a practising pathologist. During follow-up alpha-fetoprotein estimation showed a gradual decline and later became normal. CECT chest and abdomen had no evidence of any significant mediastinal/abdominal lymphadenopathy and even positron emission tomography (PET) scan of whole body revealed no active disease. The patient was asymptomatic for one and half years following surgery till he developed off and on low grade fever, hemoptysis and progressively increasing dyspnoea for which he was reinvestigated. Chest radiograph done revealed homogenous opacity in left upper and middle zone with gross mediastinal shift (Fig. 1). CECT chest had shown large, anterior and middle mediastinal masses, intracardiac mass in left atrium and left sided pleural effusion (Fig. 2). Echocardiography revealed large echogenic space occupying lesion in left atrium (Fig. 3). Other findings included small space occupying lesion in left pulmonary artery, large space occupying lesion outside the cardiac border suggestive of mediastinal mass and mild pericardial effusion with left ventricular ejection fraction (LVEF) 64%. Ultrasound abdomen did not show any retroperitoneal lymphadenopathy, but had evidence of left sided pleural effusion.

On present admission he had complaints of off and on low grade fever, hemoptysis and progressively increasing dyspnoea for four months, dizziness for 15 days and one episode of seizure followed by altered sensorium on the day of admission. On examination he was in shock (systolic blood pressure 60 mmHg) with pulse rate of 102/min, regular. Peripheries were cold and clammy, respiratory rate was 20/min and there was no lymphadenopathy. He was deeply comatosed; demonstrable focal neurological deficit and signs of meningeal irritation were absent. Heart sounds were feeble and bilateral diffuse crepitations were present. Electrocardiogram (ECG) was inconclusive because of technical error. On the basis of past history, presenting complaints and investigations, a provisional diagnosis of testicular teratoma metastasizing to heart, pleura, lungs and mediastinum without any sign of cardiac tamponade was made. Patient was immediately intubated as arterial blood gas analysis showed oxygen saturation of 60% and inotropic support was started along with intravenous fluids, antibiotic and steroids, but patient deteriorated progressively and subsequently expired within an hour of admission.

For the purpose of reaching a definitive diagnosis, the slides prepared following orchidectomy were obtained from the reporting private pathologist, restained and reviewed by two professors of pathology independently at our institution where patient was admitted before his demise. Histopathological report revealed element of mature teratoma (squamous cell, glands and neural element) along with foci of hyperchromatic cells (Fig. 4). There was also presence of Schiller-Duvall body (Fig. 5a), glands with hyperchromatic nuclei and prominent nucleoli (Fig. 5b) as seen in yolk sac tumor. A final histopathological diagnosis of non-seminomatous malignant mixed germ cell tumor (teratoma and yolk sac tumor) was therefore established. In the opinion of these pathologists probably,

foci of hyperchromatic cells were interpreted as immature element by the previous private pathologist and therefore erroneous final report.

DISCUSSION

This patient had non-seminomatous malignant mixed germ cell tumor (teratoma and yolk sac tumor), possibly stage I (postoperative CECT abdomen/chest and even PET scan were normal). Alpha-fetoprotein levels also became normal following surgery. After one and half year of quiescent period he presented with widespread metastasis to pleura, lungs, mediastinum and more strikingly to the heart.

Mature teratoma is a common component of mixed germ cell tumors (MGCTs). Mature teratoma can pursue an aggressive clinical course after puberty and metastases may contain non-teratomatous malignant germ cell tumor components. In the post-pubertal patients, yolk sac tumor is almost invariable component of MGCTs and the reported frequency of a yolk sac tumor among adult MGCTs is 44%. As seen in our patient, yolk sac tumor remains an often overlooked component of testicular germ cell tumor because of focal presence, varied and subtle morphologic pattern and finally difficult distinction from embryonal carcinoma. It has been observed that adult having yolk sac tumor as component of MGCTs usually have a high frequency of stage I disease compared to those without such a component.1 Testicular MGCTs usually present with slowly progressive testicular enlargement with or without pain or manifestations secondary to metastasis which is known to involve almost all organs of the body.2

In the presence of neoplastic disease, pericardial pain, effusion, tamponade constriction, rapid increase in heart size, new heart murmurs, ECG changes, atrial or ventricular arrhythmias, atrio-ventricular block and unexplained heart failure are suggestive of secondary invasion of the heart. The spells of dizziness, documented hypotension,

unconsciousness, suspected embolization to brain in the form of seizure and altered behaviour in presence of intracavitary mass and multiple constitutional symptoms as seen in this patient closely resembles the triad described in intracavitary tumor.4

There are few case reports of testicular tumor metastasizing to heart. Respiratory distress was the presenting feature in a 41 year old male with testicular mass which turned out to be seminoma on histopathological report. He also had intracavitatory mass in both atria causing symptomatic obstruction to blood flow.5 Superior vena cava, left brachiocephalic vein and right heart extension causing mild pulmonary embolism in addition were found in patients with testicular germ cell tumor.3 Another patient who had multiple metastasis in the retroperitoneal lymph node, both lungs as well as tumor thrombus extending from left vein to the inferior vena cava and pathological diagnosis of thrombus had revealed a picture of mature teratoma has also been reported.6

Alpha-fetoprotein (AFP), β-hCG and lactate dehydrogenase (LDH) should be obtained in suspected testicular tumor, although neither markers alone or in combination are sufficiently sensitive or specific to establish the diagnosis in the absence of histologic confirmation. Despite the refinement of radiologic imaging for retroperitoneal lymphadenopathy, 15% to 40% patients of nonseminomatous germ cell tumors (NSGCT) are still understaged. On the other hand, retroperitoneal metastasis is found in approximately 25% to 30% of patients who are judged preoperatively to have clinical stage I.7

A properly performed retroperitoneal lymph node dissection (RPLND) is a curative procedure, with rare infield recurrence and a surgical mortality of less than 1%. Approximately 20-30% of patients with normal serum tumor markers relapse during surveillance. Fewer than 10% of patients with NSGCT relapse more than 2 years after orchidectomy. Retroperitoneum is the commonest site of relapse followed by lung and other viscera. Because relapse is extremely uncommon after 2 years and rare after 5 years; periodic reevaluation is mandatory but may be annual in the fifth year and beyond.7 The above management probably determined the overall therapy in our patient but he had delayed, rare and fatal vascular and lymphatic metastasis.

Conclusion

All germ cell tumors occurring in the testes in post-pubertal males should be followed up, even if they have shown features of a mature teratoma. It is also advisable to extensively sample the resected specimen to rule out a hidden malignant counterpart.

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