Printer Friendly

Secondary malignant transformation of a primary mediastinal germ cell tumor with diffuse lymphangitic spread to the lungs. (Case Report).

Abstract: A 27-year-old man with no history of cardiopulmonary disease presented with progressive shortness of breath. He was significantly tachypneic and hypoxic, with inspiratory and expiratory wheezing. Evaluation of the chest with computed tomography revealed a large anterior mediastinal mass and interstitial thickening consistent with lymphangitic spread. Plasma [beta]-human chorionic gonadotropin level was elevated. Bronchoscopic biopsy specimen showed poorly differentiated carcinoma. Pleural fluid obtained via thoracentesis was positive for malignancy. Chemotherapy for the germ cell tumor, consisting of etoposide, ifosfamide, and cisplatin, resulted in dramatic clinical improvement and normalization of the 13-human chorionic gonadotropin level. The lymphangitic changes resolved, although the mediastinal mass persisted. A large, anterior mediastinal, mature teratoma, as well as pleural nodules with adenocarcinoma, was excised after completion of chemotherapy.


Primary germ cell tumors of the mediastinum are relatively rare an account for a small portion of all mediastinal tumors. The different subtypes of this entity are made up of seminomas and nonseminomatous germ cell tumors (ie, embryonal carcinoma, choriocarcinoma, yolk sac tumors, mixed germ cell tumors, mature and immature teratomas). We describe the case of a young man with a primary anterior mediastinal germ cell tumor who presented with respiratory distress secondary to diffuse lymphangitic spread. The germ cell tumor had secondarily transformed into a non-germ cell malignancy and metastasized to the lungs, resulting in lymphangitic spread and causing this unusual initial clinical presentation.


Germ cell tumors account for approximately 1% of all malignancies occurring in men, with the testis being the most common site of origin. Teratoma containing hair has been well recognized since at least the early 1600s from descriptions by Casper Bauhin (1560-1634) in A Book on Human Monsters and by Fabrious Heldaneus (1560-1624), sometimes called the father of German surgery. (1) As cited by Ewing, (2) Waldeyer first reported a case of an individual with a testicular teratoma with secondary malignant transformation. It was not until 1977, however, that the World Health Organization classified a germ cell neoplasm with non-germ cell elements as a teratoma with malignant transformation. (3) In adults, the anterior mediastinum is the most frequent extragonadal site of origin of nonseminomatous germ cell tumors, representing 10 to 15% of all mediastinal tumors. (4) Of those, mature teratoma is the histologic subtype in 50 to 60% of patients. The mean age of patients at presentation is 28 years. Teratomas that un dergo malignant transformation are rare, and comprise only 6% of all teratomas. Of the transformed teratomas, 95% are of the immature type.

The histology of the non-germ cell malignant elements arising from germ cell tumors most commonly includes carcinoma and various types of sarcomas. (5) The sequence of events to transformation is unclear, and the time required to undergo secondary transformation is not known. Diagnosis of mediastinal masses most commonly occurs serendipitously, through chest roentgenography performed for other reasons. Little clinical information concerning the behavior of the disease is available. Diffuse lymphangitic spread is a distinctly uncommon initial presentation of mediastinal germ cell tumors. Respiratory distress and hypoxemia secondary to diffuse involvement of the lungs delayed diagnosis in our patient because of this unusual initial presentation. Whereas the prognosis for patients with mature teratomas after excision is good, patients with malignant transformation experience recurrence rates ranging from 59 to 86%. (5,6) Teratomas with malignant transformation are usually metastatic at presentation and have a mo re aggressive clinical course than teratomas as a whole. Chemoresistance of mature teratomas is universal, and recurrence frequent if not completely excised. The non-germ cell component often does not respond to platinum-based chemotherapy. A literature review found few case reports of transformed germ cell teratomas, and none of them reported respiratory distress as the presenting symptom.


We present the case of a young man with a mature primary anterior mediastinal teratoma that had secondarily transformed into a non-germ cell tumor. His presenting symptoms with lymphangitic spread were distinctly unusual. Our report should raise awareness of this disease entity. Diagnosis may be delayed unless there is a high index of suspicion, especially in young patients with anterior mediastinal mass who present with shortness of breath that is unresponsive to initial treatment.
Table 1

Serum [beta]-human chorionic gonadotropin levels (a)

 [beta]-hCG level
Gonadotropin measurement (mIU/ml)

At diagnosis 31
After chemothempy <5
Normal value (men and nonpregnant <10

(a)[beta]-HCG, [beta]-human chorionic gonadotropin.

Accepted January 22, 2002.


(1.) Wagner RB. The history of mediastinal teratoma. Chest Surg Clin N Am 2000;10:213-222.

(2.) Ewing J. Teratoma testis and its derivatives. Surg Gynecol Obstet 1911;12:230.

(3.) Mostofi FK, Sobin LH. Histological typing of testis tumors, in International Histological Classification of Tumours. Geneva, World Health Organization, 1977.

(4.) Strollo DC, Rosado de Christenson ML, Jett JR. Primary mediastinal tumors: Part 1--tumors of the anterior mediastinum. Chest 1997;112:511-522.

(5.) Comiter CV, Kibel AS, Richie JP, Nucci MR, Renshaw AA. Prognostic features of teratomas with malignant transformation: A clinicopathological study of 21 cases. J Urol 1998;159:859-863.

(6.) Ulbright TM, Loehrer PJ, Roth LM, Einhorn LH, Williams SD, Clark SA. The development of non-germ cell malignancies within germ cell tumors: A clinicopathologic study of 11 cases. Cancer 1984;54:1824-1833.


* A germ cell neoplasm with non-germ cell elements is classified as a teratoma with malignant transformation.

* Teratomas that undergo malignant transformation comprise only 6% of all teratomas.

* The non-germ cell malignant elements arising from germ cell tumors are most commonly carcinomas and sarcomas.

* The sequence of events to malignant transformation is unclear, and the time required to secondary transformation is not known.

* Diffuse lymphangitic spread to the lungs, which our patient had, is a distinctly uncommon initial presentation of mediastinal germ cell tumors.

Case Report

A 27-year-old man with a 15 pack-year history of tobacco use presented with a 3-week history of productive cough and worsening shortness of breath. He had lost between 10 and 20 pounds during the preceding 1 to 2 months. Review of systems was negative for fevers, chills, and hemoptysis. He had no risk factors for human immunodeficiency virus infection. There were no known environmental exposures or exposure to tuberculosis. He had symptoms of chronic gastroesophageal reflux disease, and a remote diagnosis of childhood asthma. On chest x-ray, the mediastinum appeared widened and there were small, bilateral pleural effusions, as well as diffuse, bilateral interstitial infiltrates. On physical examination, his temperature was 36.5[degrees]C; blood pressure, 160/100 mm Hg; heart rate, 90 beats/min; and respiratory rate, 28 breaths/mm. In general, he appeared dyspneic. His skin was cool and diaphoretic. Head and neck examination and cardiac examination were normal. Lung examination showed good air exchange bilater ally, with diffuse inspiratory and expiratory wheezing. Abdominal examination was unremarkable. Extremities showed no cyanosis or clubbing. The patient was neurologically intact. Routine admission laboratory values were normal. The arterial blood gas values were as follows: pH, 7.31; P[CO.sub.2], 50 mm Hg; bicarbonate (H[CO.sub.3]), 30 mmol/L; [PO.sub.2] 88 mm Hg on 50% oxygen by face mask. The electrocardiogram was normal. Review of the computed tomography (CT) of the chest revealed a large, partially calcified mass in the anterior mediastinum and extensive bilateral reticulonodular opacities, as well as a rightsided pleural effusion and bulky mediastinal and hilar lymphadenopathy. Serum [beta]-human chorionic gonadotropin ([beta]-hCG) level was elevated at 31 mIU/ml. [alpha]-Fetoprotein and lactate dehydrogenase levels were normal. Testicular mass was ruled out by ultrasonographic examination. Further workup included CT of the abdomen and pelvis and magnetic resonance imaging of the head, both of which were normal. Bronchoscopy with biopsy was performed before transfer to our institution. Review of the bronchial biopsy specimen showed invasive, poorly differentiated carcinoma. Consequently, pleural fluid was obtained via thoracentesis; cytologic results were positive for malignancy. Treatment with a regimen for germ cell tumor was begun, consisting of four cycles of ifosfamide, cisplatin, and etoposide. The patient's symptoms of cough and shortness of breath had disappeared completely by the completion of chemotherapy, and he was no longer hypoxic. The pulmonary parenchymal abnormalities and lymphangitic changes had resolved, but the anterior mediastinal mass remained essentially unchanged (Fig. 1). Serum [beta]-hCG levels had normalized after the first cycle of chemotherapy, and remained normal until the conclusion of treatment (Table 1). Moderate bilateral pleural effusions remained.

Six months after initial presentation and completion of chemotherapy, the patient underwent a thoracotomy via median sternotomy. A large residual anterior mediastinal mature teratoma was excised. Multiple small, pleura-based nodules, not visible on chest CT, were sampled by biopsy. Pathologic examination revealed adenocarcinoma. There was no evidence of a residual germ cell component on examination of the pleural biopsy samples. The patient recovered from surgery and was discharged home on postoperative day 5. A few weeks later, the patient's symptoms reappeared, and his [beta]-hCG level was again elevated. Palliative chemotherapy for his recurrent disease was begun.

From the Section of Hematology/Oncology, Department of Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire.

Reprint requests to Gabriele Popp, MD, 241 Poverty Lane #2, Lebanon, NH 03766. Email:

Copyright [c] 2003 by The Southem Medical Association

COPYRIGHT 2003 Southern Medical Association
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2003, Gale Group. All rights reserved. Gale Group is a Thomson Corporation Company.

Article Details
Printer friendly Cite/link Email Feedback
Author:Dragnev, Konstantin
Publication:Southern Medical Journal
Geographic Code:1USA
Date:Jul 1, 2003
Previous Article:Septic discitis: an important cause of back pain. (Case Report).
Next Article:Orally disintegrating olanzapine for the treatment of psychotic and behavioral disturbances associated with dementia. (Case Report).

Related Articles
Splenic Angiosarcoma and Iron Deficiency Anemia in a 43-Year-Old Man.
Extragonadal germ-cell tumor: A rare differential diagnosis of a cervical lump in a young man. (Original Article).
Metastatic gastroesophageal adenocarcinoma to skeletal muscle: a unique event.
Mediastinal staging of non-small cell lung carcinoma using computed and positron-emission tomography.
Acute mediastinal widening.
Malignant gastric stromal tumor: unusual metastatic patterns. (Case Report).
Gastrointestinal metastases from breast cancer: a case report. (Case Report).
Metastatic seminoma with cervical lymphadenopathy as the initial manifestation.
A case of malignant pleural mesothelioma.
Acute respiratory distress caused by massive thymolipoma.

Terms of use | Copyright © 2018 Farlex, Inc. | Feedback | For webmasters