CASE CONFERENCES The Expert Clinician Section Editor: David Roberts, M.D.
Cough and Dyspnea Thinking beyond Pneumonia Grace Y. Lin1, Kim M. Kerr2, and Jinghong Li2 1 Department of Pathology, University of California San Diego Health System, San Diego, California; and 2Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California San Diego Health System, La Jolla, California
Keywords: dyspnea; mediastinal mass; germ cell and embryonal tumor; choriocarcinoma
In Brief A young man was hospitalized through the emergency department because of fever, productive cough, and rapidly progressive dyspnea. Physical examination and radiographic imaging revealed that this was no ordinary chest infection. A previously healthy 22-year-old man presented to the emergency department with a 5-day history of cough productive of a small volume of pink phlegm, a 2-day history of progressively worsening dyspnea, and fever. He denied any recent sick contacts, travel, or recent changes in weight. He did not recall any noteworthy chemical, occupational, or animal exposures, and he denied HIV risk factors. He was aware of two “pimples” on his scalp. On physical examination, the patient appeared to be in moderate respiratory distress at rest. The respiratory rate was 36 breaths/min, the heart rate was 130 beats/min, and the oral temperature was 38.58 C. The chest examination revealed decreased breath sounds over the left upper lung field without adventitious sounds. There was no gynecomastia. His cardiovascular, abdominal, genital, extremity, and neurologic examinations were unremarkable. Two 1-cm round, nontender pustular lesions were noted
on his scalp. Shortly after this examination was completed, his respiratory status deteriorated, and he was intubated for hypoxemic respiratory failure. Initial laboratory studies included a normal complete blood count and differential and normal markers of renal and hepatic function, except for an elevated lactate dehydrogenase (LDH) concentration of 962 U/L. A portable chest radiograph demonstrated numerous rounded opacities located throughout both lungs and obscuring the mediastinum (Figure 1). Chest computed tomography (CT) imaging revealed the presence of a large anterior mediastinal mass measuring 16 3 9 3 8 cm. The mass was associated with complete atelectasis of the left upper lobe (Figure 2A). Innumerable bilateral pulmonary nodules/ masses and enlarged bilateral hilar lymph nodes were seen (Figure 2B). A head CT scan showed two mass lesions within the brain and multiple enhancing scalp lesions. Abdominal CT imaging showed hepatomegaly with multiple round low-density lesions.
Clinical Questions What is the likely diagnosis? What is the prognosis? What are the next steps in the management?
Diagnostic Reasoning Although this man’s history was compatible with severe community-acquired pneumonia, his chest radiographic findings were not. The discovery of numerous rounded opacities in the lungs (“cannonball lesions”) prompted additional imaging. A chest CT scan showed not only lung lesions but also a large anterior mediastinal mass. The patient’s initial laboratory studies were also atypical for pneumonia. The normal white blood count and white cell differential count pointed away from an active bacterial infection. The markedly elevated LDH, considered in the context of an anterior mediastinal mass, strongly suggested a malignancy with poor prognosis (1). After the patient was intubated and stabilized, attention was turned to consideration of the diagnosis of the mediastinal mass. The differential diagnosis for anterior mediastinal masses includes thymoma, lymphoma, thyroid lesions, and germ cell tumors (2). Thyroid lesions arising in the anterior mediastinum are usually benign and asymptomatic. Thymoma is the most common primary neoplasm of anterior mediastinum and is sometimes associated with parathymic syndromes, such as myasthenia gravis. Slowly growing metastases to the pleura or pericardium
(Received in original form July 15, 2013; accepted in final form September 23, 2013 ) Correspondence and requests for reprints should be addressed to Jinghong Li, M.D., Ph.D., Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California San Diego Health System, La Jolla, CA 92037. E-mail: [email protected] Ann Am Thorac Soc Vol 10, No 6, pp 693–696, Dec 2013 Copyright © 2013 by the American Thoracic Society DOI: 10.1513/AnnalsATS.201307-225CR Internet address: www.atsjournals.org
Case Conferences: The Expert Clinician
693
CASE CONFERENCES Diagnostic Evaluation
Figure 1. Initial portable chest X-ray with multifocal, rounded opacities throughout both lungs, with higher attenuation than expected for pneumonia.
are well-recognized manifestations of thymoma; however, synchronous metastases to lung are exceedingly rare. Lymphoma is the second most common anterior mediastinal mass and may be associated with constitutional symptoms. Hodgkin disease in particular may present with mediastinal and concomitant lung involvement. Germ cell tumors without primary testicular involvement are classified as extragonadal and are rare, accounting for only 2 to 5% of all germ cell tumors. The anterior mediastinum is the most common extragonadal site. Germ cell tumors account for up to 15% of anterior mediastinal masses in young adults. The majority (z80%) are benign teratomas and occur in both men and women.
The remainder (z20%) are malignant and are found predominantly in young men. Malignant germ cell tumors include seminomas and nonseminomas. Nonseminomatous germ cell tumors are further classified as malignant teratomas, embryonal carcinomas, endodermal sinus tumors (yolk sac tumors), choriocarcinomas, and mixed germ cell tumors. Regardless of the site of origin, germ cell tumors commonly metastasize to lung. On the basis of those considerations, lymphoma and germ cell tumor were considered the most likely diagnostic possibilities for this patient. Our diagnostic assessment was tailored accordingly.
Figure 2. (A) Chest CT with a large anterior mediastinal mass measuring 16 3 9 3 8 cm, causing complete atelectasis of the left upper lobe. (B) Innumerable bilateral pulmonary nodules/masses and enlarged bilateral hilar lymph nodes.
694
A testicular ultrasound examination was normal. Serological evaluation revealed a normal a-fetoprotein (AFP) level and a markedly elevated human chorionic gonadotrophin b subunit (b-HCG) level (58,227 mIU/ml). Bronchoscopy disclosed a mass obstructing the left upper lobe. Cytologic specimens obtained from the airways were nondiagnostic. A CT-guided fine-needle aspiration of his anterior mediastinal mass demonstrated large anaplastic malignant cells with overlapping nuclei and prominent, multiple nucleoli. Most cells had single nuclei, but multinucleated cells were also identified on direct smears (Figure 3A, arrow) and on cell block (Figure 3B, arrow). By immunohistochemical staining, the tumor cells were positive for pankeratin, which is a marker for carcinomas. The tumor was also positive for SALL-4 (Figure 3C), which was recently characterized as an immunohistochemical marker for germ cell tumors and has been reported to be positive in seminomas, embryonal carcinomas, endodermal sinus tumors, choriocarcinomas, and teratomas (3). Positive staining for b-HCG (Figure 3D) was seen in both the mononucleated and multinucleated cells, consistent with mononucleated trophoblastic cells and syncytiotrophoblasts of choriocarcinoma (4). The tumor cells were negative for typical markers of embryonal carcinomas (CD30, Oct3/4), seminomas (CD117/c-kit, Oct3/4, placental alkaline phosphatase), and endodermal sinus tumors (AFP) (4, 5). The cytologic appearance and the immunohistochemical staining pattern of the aspirated cells was most consistent with choriocarcinoma. Because the fine-needle aspirate specimen may not have been representative of the entire mass, a mixed germ cell tumor could not be completely excluded. Pure choriocarcinoma of the mediastinum is rare and represents 2.5 to 5% of mediastinal germ cell tumors (6). Most nonseminomatous germ cell tumors of the mediastinum present with symptoms associated with a local mass effect and include cough, dyspnea, stridor, dysphagia, and superior vena cava syndrome (7). Similarly, if the location and size of the mass produce partial or complete lobar obstruction, postobstructive pneumonia can occur, as was observed in this patient.
AnnalsATS Volume 10 Number 6 | December 2013
CASE CONFERENCES residual disease may be performed whenever feasible in patients who have negative levels of serum tumor markers after chemotherapy (10). Although the treatment of extragonadal germ cell tumors is similar to that for testicular germ cell tumors, patients with extragonadal germ cell tumors have a worse prognosis. Only 19% of patients achieve a complete response after chemotherapy, and the 5-year survival rate is 45% (7).
Final Diagnosis Malignant nonseminomatous germ cell tumor, consistent with choriocarcinoma. The findings could represent either a pure choriocarcinoma or a choriocarcinoma component of a mixed germ cell tumor. Figure 3. (A, B). A mixed population of highly anaplastic cells with single and multiple nuclei (arrows) per cell in smears (A, Diff-Quick stain, 3400) and cell block (B, hematoxylin and eosin stain, 3400). By immunohistochemical staining, the tumor cells are positive for pankeratin (not shown), SALL-4 (C, 3400) and human chorionic gonadotrophin b subunit (D, 3400) but negative for pan-LCA, CD117, Oct3/4, placental alkaline phosphatase, CD30, and a-fetoprotein (not shown).
Although the two pustular scalp lesions were noted on the patient’s initial physical examination, their relationship to the presenting symptoms was not appreciated until a radiologist saw them on a head CT scan and suggested that they were metastases. Had the significance of the skin lesions been recognized earlier, a skin biopsy might have led to an expedited diagnosis.
Prognosis and Management A staging system has been developed for germ cell tumors arising from gonadal structures; however, because of infrequency, no staging system has been described specifically for anterior mediastinal germ cell tumors. A prognostic factor–based staging system is used instead (1). Tumor markers provide diagnostic and prognostic information. In terms of diagnostic information, this patient had significantly elevated serum concentrations of b-HCG, which strongly favors the diagnosis of choriocarcinoma. Nonseminomatous germ cell tumors produce high levels of b-HCG, AFP, or both. Choriocarcinoma and embryonal Case Conferences: The Expert Clinician
carcinoma usually produce high levels of b-HCG. Less than 10% of patients with seminoma have an elevated b-HCG level, and the level is usually much lower. Endodermal sinus tumors induce elevation of AFP. LDH is a nonspecific marker, but its level correlates well with the tumor burden. Predictors for poor prognosis of nonseminomatous germ cell tumors include primary mediastinal tumors, nonpulmonary visceral metastases, and elevated serum markers, including AFP greater than 10,000 ng/ml, or b-HCG greater than 50,000 mIU/ml, or LDH more than 10 times the upper limit of normal (1). This patient unfortunately had multiple poor prognostic factors. Chemotherapy should be initiated at the time of diagnosis. Standard therapy is four courses of BEP (bleomycin, etoposide, and cisplatin) (8). A randomized study comparing four courses of BEP with four courses of VIP (etoposide, ifosfamide, and cisplatin) showed similar responses to the two regimens in patients with disseminated extragonadal germ cell tumors (9). VIP is preferred by some oncologists due to the pulmonary toxicity of bleomycin. Others use BEP without the bleomycin (EP). After completion of chemotherapy, surgical resection of
Follow-up The patient underwent cisplatin-based chemotherapy. He received one cycle of EP therapy (etoposide, cisplatin) without bleomycin due to his respiratory failure requiring mechanical ventilation, followed by three cycles of VIP. After the fourth cycle, the b-HCG level was reduced to 36 mIU/ml but was never undetectable. Three weeks later, his b-HCG level was again rising. He received additional palliative chemotherapy and died 8 months after diagnosis.
Insights
d
d
d
The differential diagnosis of an anterior mediastinal mass includes thymoma, lymphoma, thyroid lesions, and germ cell tumors. Diagnostic procedures for an anterior mediastinal mass, including tissue diagnosis and serological evaluation, should be performed rapidly. Despite aggressive therapeutic approaches, including cisplatin-based chemotherapy, extragonadal germ cell tumors carry a worse prognosis compared with gonadal germ cell tumors. n
Author disclosures are available with the text of this article at www.atsjournals.org.
695
CASE CONFERENCES
References 1 International Germ Cell Consensus Classification: a prognostic factorbased staging system for metastatic germ cell cancers. International Germ Cell Cancer Collaborative Group. J Clin Oncol 1997;15: 594–603. 2 Davis RD Jr, Oldham HN Jr, Sabiston DC Jr. Primary cysts and neoplasms of the mediastinum: recent changes in clinical presentation, methods of diagnosis, management, and results. Ann Thorac Surg 1987;44:229–237. 3 Cao D, Li J, Guo CC, Allan RW, Humphrey PA. SALL4 is a novel diagnostic marker for testicular germ cell tumors. Am J Surg Pathol 2009;33:1065–1077. 4 Woodward PJ, Heidenreich A, Looijenga LHJ, Oosterhuis JW, McLeod DG, Moller H, Manivel JC, Mostofi FK, Hailemariam S, Parkinson MC, et al. Germ cell tumours. In: Eble JN, Sauter G, Epstein JI, Sesterhenn IA, editors. Pathology and genetics of tumours of the urinary system and male genital organs. Lyon, France: IARC Press; 2004. pp. 221–249. 5 Gopalan A, Dhall D, Olgac S, Fine SW, Korkola JE, Houldsworth J, Chaganti RS, Bosl GJ, Reuter VE, Tickoo SK. Testicular mixed germ cell tumors: a morphological and immunohistochemical study using stem cell markers, OCT3/4, SOX2 and GDF3, with emphasis on morphologically difficult-to-classify areas. Mod Pathol 2009;22: 1066–1074.
696
6 Wick MR, Zettl A, Chan JKC, Bokemeyer C, Perlman EJ, Marx A. Choriocarcinoma. In: Travis W, Brambilla E, Muller-Hermelink ¨ H, et al. editors. Tumours of the lung, thymus, and heart. Pathology and genetics. Lyon, France: IARC Press; 2004. pp. 209–210. 7 Bokemeyer C, Nichols CR, Droz JP, Schmoll HJ, Horwich A, Gerl A, Fossa SD, Beyer J, Pont J, Kanz L, et al. Extragonadal germ cell tumors of the mediastinum and retroperitoneum: results from an international analysis. J Clin Oncol 2002;20:1864–1873. 8 Williams SD, Birch R, Einhorn LH, Irwin L, Greco FA, Loehrer PJ. Treatment of disseminated germ-cell tumors with cisplatin, bleomycin, and either vinblastine or etoposide. N Engl J Med 1987; 316:1435–1440. 9 Nichols CR, Catalano PJ, Crawford ED, Vogelzang NJ, Einhorn LH, Loehrer PJ. Randomized comparison of cisplatin and etoposide and either bleomycin or ifosfamide in treatment of advanced disseminated germ cell tumors: an Eastern Cooperative Oncology Group, Southwest Oncology Group, and Cancer and Leukemia Group B Study. J Clin Oncol 1998;16:1287–1293. 10 Kesler KA, Rieger KM, Hammoud ZT, Kruter LE, Perkins SM, Turrentine MW, Schneider BP, EinhornLH, Brown JW. A 25-year single institution experience with surgery for primary mediastinal nonseminomatous germ cell tumors. Ann Thorac Surg 2008;85: 371–378.
AnnalsATS Volume 10 Number 6 | December 2013
Cough and Dyspnea Thinking beyond Pneumonia Grace Y. Lin1, Kim M. Kerr2, and Jinghong Li2 1 Department of Pathology, University of California San Diego Health System, San Diego, California; and 2Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California San Diego Health System, La Jolla, California
Keywords: dyspnea; mediastinal mass; germ cell and embryonal tumor; choriocarcinoma
In Brief A young man was hospitalized through the emergency department because of fever, productive cough, and rapidly progressive dyspnea. Physical examination and radiographic imaging revealed that this was no ordinary chest infection. A previously healthy 22-year-old man presented to the emergency department with a 5-day history of cough productive of a small volume of pink phlegm, a 2-day history of progressively worsening dyspnea, and fever. He denied any recent sick contacts, travel, or recent changes in weight. He did not recall any noteworthy chemical, occupational, or animal exposures, and he denied HIV risk factors. He was aware of two “pimples” on his scalp. On physical examination, the patient appeared to be in moderate respiratory distress at rest. The respiratory rate was 36 breaths/min, the heart rate was 130 beats/min, and the oral temperature was 38.58 C. The chest examination revealed decreased breath sounds over the left upper lung field without adventitious sounds. There was no gynecomastia. His cardiovascular, abdominal, genital, extremity, and neurologic examinations were unremarkable. Two 1-cm round, nontender pustular lesions were noted
on his scalp. Shortly after this examination was completed, his respiratory status deteriorated, and he was intubated for hypoxemic respiratory failure. Initial laboratory studies included a normal complete blood count and differential and normal markers of renal and hepatic function, except for an elevated lactate dehydrogenase (LDH) concentration of 962 U/L. A portable chest radiograph demonstrated numerous rounded opacities located throughout both lungs and obscuring the mediastinum (Figure 1). Chest computed tomography (CT) imaging revealed the presence of a large anterior mediastinal mass measuring 16 3 9 3 8 cm. The mass was associated with complete atelectasis of the left upper lobe (Figure 2A). Innumerable bilateral pulmonary nodules/ masses and enlarged bilateral hilar lymph nodes were seen (Figure 2B). A head CT scan showed two mass lesions within the brain and multiple enhancing scalp lesions. Abdominal CT imaging showed hepatomegaly with multiple round low-density lesions.
Clinical Questions What is the likely diagnosis? What is the prognosis? What are the next steps in the management?
Diagnostic Reasoning Although this man’s history was compatible with severe community-acquired pneumonia, his chest radiographic findings were not. The discovery of numerous rounded opacities in the lungs (“cannonball lesions”) prompted additional imaging. A chest CT scan showed not only lung lesions but also a large anterior mediastinal mass. The patient’s initial laboratory studies were also atypical for pneumonia. The normal white blood count and white cell differential count pointed away from an active bacterial infection. The markedly elevated LDH, considered in the context of an anterior mediastinal mass, strongly suggested a malignancy with poor prognosis (1). After the patient was intubated and stabilized, attention was turned to consideration of the diagnosis of the mediastinal mass. The differential diagnosis for anterior mediastinal masses includes thymoma, lymphoma, thyroid lesions, and germ cell tumors (2). Thyroid lesions arising in the anterior mediastinum are usually benign and asymptomatic. Thymoma is the most common primary neoplasm of anterior mediastinum and is sometimes associated with parathymic syndromes, such as myasthenia gravis. Slowly growing metastases to the pleura or pericardium
(Received in original form July 15, 2013; accepted in final form September 23, 2013 ) Correspondence and requests for reprints should be addressed to Jinghong Li, M.D., Ph.D., Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California San Diego Health System, La Jolla, CA 92037. E-mail: [email protected] Ann Am Thorac Soc Vol 10, No 6, pp 693–696, Dec 2013 Copyright © 2013 by the American Thoracic Society DOI: 10.1513/AnnalsATS.201307-225CR Internet address: www.atsjournals.org
Case Conferences: The Expert Clinician
693
CASE CONFERENCES Diagnostic Evaluation
Figure 1. Initial portable chest X-ray with multifocal, rounded opacities throughout both lungs, with higher attenuation than expected for pneumonia.
are well-recognized manifestations of thymoma; however, synchronous metastases to lung are exceedingly rare. Lymphoma is the second most common anterior mediastinal mass and may be associated with constitutional symptoms. Hodgkin disease in particular may present with mediastinal and concomitant lung involvement. Germ cell tumors without primary testicular involvement are classified as extragonadal and are rare, accounting for only 2 to 5% of all germ cell tumors. The anterior mediastinum is the most common extragonadal site. Germ cell tumors account for up to 15% of anterior mediastinal masses in young adults. The majority (z80%) are benign teratomas and occur in both men and women.
The remainder (z20%) are malignant and are found predominantly in young men. Malignant germ cell tumors include seminomas and nonseminomas. Nonseminomatous germ cell tumors are further classified as malignant teratomas, embryonal carcinomas, endodermal sinus tumors (yolk sac tumors), choriocarcinomas, and mixed germ cell tumors. Regardless of the site of origin, germ cell tumors commonly metastasize to lung. On the basis of those considerations, lymphoma and germ cell tumor were considered the most likely diagnostic possibilities for this patient. Our diagnostic assessment was tailored accordingly.
Figure 2. (A) Chest CT with a large anterior mediastinal mass measuring 16 3 9 3 8 cm, causing complete atelectasis of the left upper lobe. (B) Innumerable bilateral pulmonary nodules/masses and enlarged bilateral hilar lymph nodes.
694
A testicular ultrasound examination was normal. Serological evaluation revealed a normal a-fetoprotein (AFP) level and a markedly elevated human chorionic gonadotrophin b subunit (b-HCG) level (58,227 mIU/ml). Bronchoscopy disclosed a mass obstructing the left upper lobe. Cytologic specimens obtained from the airways were nondiagnostic. A CT-guided fine-needle aspiration of his anterior mediastinal mass demonstrated large anaplastic malignant cells with overlapping nuclei and prominent, multiple nucleoli. Most cells had single nuclei, but multinucleated cells were also identified on direct smears (Figure 3A, arrow) and on cell block (Figure 3B, arrow). By immunohistochemical staining, the tumor cells were positive for pankeratin, which is a marker for carcinomas. The tumor was also positive for SALL-4 (Figure 3C), which was recently characterized as an immunohistochemical marker for germ cell tumors and has been reported to be positive in seminomas, embryonal carcinomas, endodermal sinus tumors, choriocarcinomas, and teratomas (3). Positive staining for b-HCG (Figure 3D) was seen in both the mononucleated and multinucleated cells, consistent with mononucleated trophoblastic cells and syncytiotrophoblasts of choriocarcinoma (4). The tumor cells were negative for typical markers of embryonal carcinomas (CD30, Oct3/4), seminomas (CD117/c-kit, Oct3/4, placental alkaline phosphatase), and endodermal sinus tumors (AFP) (4, 5). The cytologic appearance and the immunohistochemical staining pattern of the aspirated cells was most consistent with choriocarcinoma. Because the fine-needle aspirate specimen may not have been representative of the entire mass, a mixed germ cell tumor could not be completely excluded. Pure choriocarcinoma of the mediastinum is rare and represents 2.5 to 5% of mediastinal germ cell tumors (6). Most nonseminomatous germ cell tumors of the mediastinum present with symptoms associated with a local mass effect and include cough, dyspnea, stridor, dysphagia, and superior vena cava syndrome (7). Similarly, if the location and size of the mass produce partial or complete lobar obstruction, postobstructive pneumonia can occur, as was observed in this patient.
AnnalsATS Volume 10 Number 6 | December 2013
CASE CONFERENCES residual disease may be performed whenever feasible in patients who have negative levels of serum tumor markers after chemotherapy (10). Although the treatment of extragonadal germ cell tumors is similar to that for testicular germ cell tumors, patients with extragonadal germ cell tumors have a worse prognosis. Only 19% of patients achieve a complete response after chemotherapy, and the 5-year survival rate is 45% (7).
Final Diagnosis Malignant nonseminomatous germ cell tumor, consistent with choriocarcinoma. The findings could represent either a pure choriocarcinoma or a choriocarcinoma component of a mixed germ cell tumor. Figure 3. (A, B). A mixed population of highly anaplastic cells with single and multiple nuclei (arrows) per cell in smears (A, Diff-Quick stain, 3400) and cell block (B, hematoxylin and eosin stain, 3400). By immunohistochemical staining, the tumor cells are positive for pankeratin (not shown), SALL-4 (C, 3400) and human chorionic gonadotrophin b subunit (D, 3400) but negative for pan-LCA, CD117, Oct3/4, placental alkaline phosphatase, CD30, and a-fetoprotein (not shown).
Although the two pustular scalp lesions were noted on the patient’s initial physical examination, their relationship to the presenting symptoms was not appreciated until a radiologist saw them on a head CT scan and suggested that they were metastases. Had the significance of the skin lesions been recognized earlier, a skin biopsy might have led to an expedited diagnosis.
Prognosis and Management A staging system has been developed for germ cell tumors arising from gonadal structures; however, because of infrequency, no staging system has been described specifically for anterior mediastinal germ cell tumors. A prognostic factor–based staging system is used instead (1). Tumor markers provide diagnostic and prognostic information. In terms of diagnostic information, this patient had significantly elevated serum concentrations of b-HCG, which strongly favors the diagnosis of choriocarcinoma. Nonseminomatous germ cell tumors produce high levels of b-HCG, AFP, or both. Choriocarcinoma and embryonal Case Conferences: The Expert Clinician
carcinoma usually produce high levels of b-HCG. Less than 10% of patients with seminoma have an elevated b-HCG level, and the level is usually much lower. Endodermal sinus tumors induce elevation of AFP. LDH is a nonspecific marker, but its level correlates well with the tumor burden. Predictors for poor prognosis of nonseminomatous germ cell tumors include primary mediastinal tumors, nonpulmonary visceral metastases, and elevated serum markers, including AFP greater than 10,000 ng/ml, or b-HCG greater than 50,000 mIU/ml, or LDH more than 10 times the upper limit of normal (1). This patient unfortunately had multiple poor prognostic factors. Chemotherapy should be initiated at the time of diagnosis. Standard therapy is four courses of BEP (bleomycin, etoposide, and cisplatin) (8). A randomized study comparing four courses of BEP with four courses of VIP (etoposide, ifosfamide, and cisplatin) showed similar responses to the two regimens in patients with disseminated extragonadal germ cell tumors (9). VIP is preferred by some oncologists due to the pulmonary toxicity of bleomycin. Others use BEP without the bleomycin (EP). After completion of chemotherapy, surgical resection of
Follow-up The patient underwent cisplatin-based chemotherapy. He received one cycle of EP therapy (etoposide, cisplatin) without bleomycin due to his respiratory failure requiring mechanical ventilation, followed by three cycles of VIP. After the fourth cycle, the b-HCG level was reduced to 36 mIU/ml but was never undetectable. Three weeks later, his b-HCG level was again rising. He received additional palliative chemotherapy and died 8 months after diagnosis.
Insights
d
d
d
The differential diagnosis of an anterior mediastinal mass includes thymoma, lymphoma, thyroid lesions, and germ cell tumors. Diagnostic procedures for an anterior mediastinal mass, including tissue diagnosis and serological evaluation, should be performed rapidly. Despite aggressive therapeutic approaches, including cisplatin-based chemotherapy, extragonadal germ cell tumors carry a worse prognosis compared with gonadal germ cell tumors. n
Author disclosures are available with the text of this article at www.atsjournals.org.
695
CASE CONFERENCES
References 1 International Germ Cell Consensus Classification: a prognostic factorbased staging system for metastatic germ cell cancers. International Germ Cell Cancer Collaborative Group. J Clin Oncol 1997;15: 594–603. 2 Davis RD Jr, Oldham HN Jr, Sabiston DC Jr. Primary cysts and neoplasms of the mediastinum: recent changes in clinical presentation, methods of diagnosis, management, and results. Ann Thorac Surg 1987;44:229–237. 3 Cao D, Li J, Guo CC, Allan RW, Humphrey PA. SALL4 is a novel diagnostic marker for testicular germ cell tumors. Am J Surg Pathol 2009;33:1065–1077. 4 Woodward PJ, Heidenreich A, Looijenga LHJ, Oosterhuis JW, McLeod DG, Moller H, Manivel JC, Mostofi FK, Hailemariam S, Parkinson MC, et al. Germ cell tumours. In: Eble JN, Sauter G, Epstein JI, Sesterhenn IA, editors. Pathology and genetics of tumours of the urinary system and male genital organs. Lyon, France: IARC Press; 2004. pp. 221–249. 5 Gopalan A, Dhall D, Olgac S, Fine SW, Korkola JE, Houldsworth J, Chaganti RS, Bosl GJ, Reuter VE, Tickoo SK. Testicular mixed germ cell tumors: a morphological and immunohistochemical study using stem cell markers, OCT3/4, SOX2 and GDF3, with emphasis on morphologically difficult-to-classify areas. Mod Pathol 2009;22: 1066–1074.
696
6 Wick MR, Zettl A, Chan JKC, Bokemeyer C, Perlman EJ, Marx A. Choriocarcinoma. In: Travis W, Brambilla E, Muller-Hermelink ¨ H, et al. editors. Tumours of the lung, thymus, and heart. Pathology and genetics. Lyon, France: IARC Press; 2004. pp. 209–210. 7 Bokemeyer C, Nichols CR, Droz JP, Schmoll HJ, Horwich A, Gerl A, Fossa SD, Beyer J, Pont J, Kanz L, et al. Extragonadal germ cell tumors of the mediastinum and retroperitoneum: results from an international analysis. J Clin Oncol 2002;20:1864–1873. 8 Williams SD, Birch R, Einhorn LH, Irwin L, Greco FA, Loehrer PJ. Treatment of disseminated germ-cell tumors with cisplatin, bleomycin, and either vinblastine or etoposide. N Engl J Med 1987; 316:1435–1440. 9 Nichols CR, Catalano PJ, Crawford ED, Vogelzang NJ, Einhorn LH, Loehrer PJ. Randomized comparison of cisplatin and etoposide and either bleomycin or ifosfamide in treatment of advanced disseminated germ cell tumors: an Eastern Cooperative Oncology Group, Southwest Oncology Group, and Cancer and Leukemia Group B Study. J Clin Oncol 1998;16:1287–1293. 10 Kesler KA, Rieger KM, Hammoud ZT, Kruter LE, Perkins SM, Turrentine MW, Schneider BP, EinhornLH, Brown JW. A 25-year single institution experience with surgery for primary mediastinal nonseminomatous germ cell tumors. Ann Thorac Surg 2008;85: 371–378.
AnnalsATS Volume 10 Number 6 | December 2013
