Extra gonadal germ cell tumors have variable clinical presentations and locations. We report a case of an extra-gonadal germ cell tumor in a 26-year-old male who presented with chest pain. Imaging revealed a large pericardial effusion with underlying mass invading the pericardium. Pericardial effusion is an extremely rare initial site of diagnosis or site of metastasis for malignancy. This case illustrates the importance of a thorough history and physical examination, broad differential diagnosis, and to keep in mind serious complications from rare presentations of disease. INTRODUCTION embryogenesis or due to physiological extra-gonadal distribu- First described in the mid-19th century, extra-gonadal germ cell tion of germ cells to provide hematologic and immunologic tumors (EGGCT) are neoplasms displaying histological, serological information . The most common sites of extra-gonadal pres- and cytogenetic characteristics consistent with gonadal origin, entation include (from most to least prevalent) the mediasti- but located outside the gonads . This subset of germ cell can- num, retroperitoneum, pineal gland and sacral area. Very rarely cers comprises of ~2–5% of all malignant germ cell tumors . do such neoplasms arise in the prostate, vagina, orbit, liver or Similar to gonadal tumors, EGGCT neoplasms can occur in several the gastrointestinal tract . Published series of >600 patients different histological patterns which display the progression of have shown that most common clinical presentations include normal embryonic development. These tumors can broadly be dyspnea (25%), chest pain (23%), cough (17%), fever (13%), weight classiﬁed into seminomatous and nonseminomatous germ cell loss (11%) and superior vena cava syndrome (6%). Rare cases tumors. Seminomatous germ cell tumors mainly include germi- (<2%) cases have presented with hemoptysis, hoarseness or noma and dysgerminoma whereas the nonseminomatous coun- dysphagia . Median age of presentation varies by the site of terpart includes endodermal sinus tumor, yolk sac tumor, origin with a median age being 28–33 for retroperitoneal tumors embryonal carcinoma, choriocarcinoma and teratoma . and 30–41 for mediastinal neoplasms. Tumor markers that are Current hypotheses regarding presentation of EGGCT revolve commonly elevated include alpha-fetoprotein (AFP), beta-human around either aberrancy in migration of germ cells during chorionic gonadotropin (b-HCG), lactate dehydrogenase (LDH) and Received: September 15, 2017. Revised: September 25, 2017. Accepted: November 29, 2017 © The Author(s) 2017. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/ licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact email@example.com Downloaded from https://academic.oup.com/omcr/article-abstract/2018/2/omx097/4898986 by Ed 'DeepDyve' Gillespie user on 16 March 2018 Pericardial effusion as an atypical initial presentation 55 alkaline phosphatase. Extragonadal seminomatous tumors usu- and OCT-4 negative. Further workup, including testicular ultra- ally present with an elevated b-HCG and LDH whereas elevations sound, CT abdomen and pelvis, and MRI brain showed no evi- in b-HCG and AFP are commonly seen with extragonadal nonse- dence of intratesticular tumor or metastatic foci, conﬁrming minomatous neoplasms. Although mediastinal germ cell tumors the diagnosis of an EGGCT. The patient was promptly started have been well described, invasion into the pericardium and on chemotherapy with bleomycin, etoposide and cisplatin (BEP) resultant malignant pericardial effusion is a rare phenomenon with the intention of surgical resection following reduction in which has been the topic of sporadic case reports involving the size of the tumor. Pre-chemotherapy pulmonary function mainly pediatric patients [6, 7]. We present a rare care of intraper- tests (PFTs) revealed a moderate restrictive pattern, and subse- icardial EGGCT and presented concomitantly with malignant peri- quent PFTs showed no evidence of bleomycin-induced lung cardial effusion. injury. On completion of four cycles of BEP, a CT scan of the chest was done which showed interval decrease in size of the medias- tinal mass with a new spiculated left upper lobe nodule con- CASE REPORT cerning for metastatic disease (Fig. 2). Cardiac MRI showed A 26-year-old white construction worker with a remote history pericardial and epicardial fat invasion along the anterior right of asthma presented to the emergency department with a chief ventricle abutting the main and left pulmonary arteries without complaint of chest pain. He had been seen 2 months prior with evidence of myocardial invasion. He underwent cardiothoracic similar chest pain which was attributed to musculoskeletal surgery for tumor resection, which revealed tumor invasion into injury versus costochondritis after acute coronary syndrome the pericardium adherent to the epicardium, invasion into the was ruled out, and he was discharged with non-steroidal anti- left atrial appendage, invasion into the left hilum and invasion inﬂammatory medications (NSAIDs). On re-evaluation two in the left pulmonary artery; and underwent tumor resection, months later, he also reported associated dyspnea on exertion, lingular-sparing left upper lobectomy, pericardial resection with fever, night sweats, and weight loss. A computed tomography Gore-tex mesh reconstruction, left atrial resection and lung (CT) scan of the chest showed a large 10.5 cm mediastinal mass adhesionolysis. compressing the main pulmonary artery with a large pericar- Post-operatively, his course was complicated by acute hyp- dial effusion with invasion into the pericardium (Fig. 1). oxic respiratory failure secondary to acute respiratory distress Transthoracic echocardiogram showed a large pericardial effu- syndrome (ARDS), bleomycin-induced lung toxicity, and multi- sion without tamponade physiology. He underwent pericardio- drug resistant pseudomonal pneumonia requiring intubation centesis with pericardial drain placement and biopsy of the and mechanical ventilation. He was treated with high-dose pericardium and intrapericardial mass. On the ﬁfth day of hos- steroids and N-acetylcysteine followed by imatinib, restrictive pitalization, the patient developed sudden onset dyspnea with FiO ARDSNET mechanical ventilation, and broad spectrum associated hypoxia. CT angiogram of the chest to assess for antibiotics. He continued to deteriorate, and extracorporeal life acute pulmonary embolism was negative, but did show pro- support management (VV-ECMO) was initiated on post- gressive compression of the pulmonary vasculature with 95% operative Day 11. His overall prognosis remained poor without stenosis of the main pulmonary artery. suggestion of lung recovery after a prolonged period of VV- The patient underwent one fraction of emergent radiation ECMO. Multiple goals of care discussions with the patient and therapy with symptomatic improvement. Labs revealed ele- family resulted in the patient opting to pursue comfort care, vated AFP (341), elevated LDH (742), and normal hCG, CEA, and and he passed away comfortably on post-operative Day 50. beta-2 microglobulin levels (Table 1). Cytology was consistent with a malignant pericardial effusion, and pathology resulted as a mixed malignant germ cell tumor with yolk sac tumor DISCUSSION (70%), embryonal carcinoma (20%) and mature teratomatous This case is an example of a nonseminomatous extragonadal component (10%). Immunohistochemistry (IHC) showed C-kit germ cell tumor initially presenting as chest pain with a peri- positive, SALL-4 negative, Calretinin negative, CD30 negative cardial invasion and associated effusion. In young patients such as this one, musculoskeletal chest pain is a common eti- ology of chest pain, especially in patients without cardiovascu- lar risk factors. In addition to thorough cardiac workup to evaluate for life threatening etiologies of chest pain, imaging with echocardiogram and CT scan are important in identifying pericardial or mediastinal mass lesions, especially in patients in whom the history suggests malignancy may be a possibility. There are numerous malignancies which can be found in the mediastinum, and the differential diagnosis is affected by the area of the mediastinum (anterior, middle or posterior) in which the tumor is found . The differential diagnosis of anterior medi- astinal masses is quite broad, encompassing thymic lesions (most common), germ cell tumors (seminomas, nonseminomas, or benign such as dermoid cysts), teratomas, lymphomas and ectopic thyroid . For mediastinal germ cell tumors, nonsemino- matous germ cell tumors have the lowest 5-year survival rate (45–48%) , far less than seminomas or teratomas. A review of the literature reveals that a pericardial effusion is an extremely rare initial site of diagnosis or site of metastasis for Figure 1: CT chest with IV contrast on presentation, showing mediastinal mass of 10 cm with compression of main and left pulmonary arteries. malignancy. There have been sporadic case reports of a variety of Downloaded from https://academic.oup.com/omcr/article-abstract/2018/2/omx097/4898986 by Ed 'DeepDyve' Gillespie user on 16 March 2018 56 W.P. Skelton et al. Table 1: International Germ Cell Cancer Collaborative Group (IGCCCG) risk stratiﬁcation system for nonseminomatous germ cell tumors Primary tumor site Serum beta-hCG (mIU/ Serum AFP (ng/ LDH mL) mL) Δ Δ Good risk Testicular or retroperitoneal Beta-hCG < 5000 AFP < 1000 LDH < 1.5 × ULN Intermediate Testicular or retroperitoneal Beta-hCG 5000–50 000 AFP 1000–10 000 LDH 1.5 to 10 × risk ULN Poor risk Mediastinal primary with or without metastases Beta-hCG > 50 000 Serum AFP > LDH > 10 × ULN or 10 000 metastases to organs other than the lungs and/or LN AFP, alpha-fetoprotein; beta-hCG, beta-human chorionic gonadotropin; LDH, lactic dehydrogenase; ULN, upper limit of normal; LN, lymph nodes; mIU/mL, milliinter- national units/mL. Indicates risk variables demonstrated by our patient’s tumor. Adapted from International Germ Cell Cancer Collaborative Group. International Germ Cell Consensus Classiﬁcation: a prognostic factor-based staging system for metastatic germ cell cancers. J Clin Oncol. 1997;15:594–603. FUNDING STATEMENT This research did not receive any speciﬁc grant from funding agencies in the public, commercial, or not-for-proﬁt sectors. ETHICAL APPROVAL N/A. CONSENT Written informed consent was obtained from the patient for publication of this case report. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request. Figure 2: CT chest with IV contrast after cytoreductive radiation therapy and GUARANTOR four cycles of BEP chemotherapy. Size reduction in the mass and a lesser mass effect on pulmonary vasculature is appreciated. Dr Long H. Dang, MD, PhD. tumors involving the pericardium, most frequently teratomas. REFERENCES After teratomas, a multitude of tumors have been reported to 1. Utz DC, Buscemi MK. Extragonadal testicular tumors. J Urol cause pericardial effusions, including paraganglioma, leukemia, 1971;105:271–4. schwannoma, carcinoid tumor, primitive neuroectodermal tumor, 2. Pottern LM, Goedert JJ. Epidemiology of testicular cancer. In: rhabdoid tumor, pheochromocytoma, melanoma and extragona- Javadpour N, ed. Principles and Management of Testicular dal germ cell tumors [6, 9, 10]. It is important to that all of these, Cancer. New York: Thieme, 1986,107–19. including nonseminomatous germ cell tumors, are extremely rare 3. Schmoll HJ. Extragonadal germ cell tumors. Ann Oncol 2002; causes of pericardial effusion, with none of these having been 13:265–72. shown to cause more than a handful of cases via literature review 4. Bokemeyer C, Nichols CR, Droz JP, Schmoll HJ, Horwich A, of case reports, retrospective analyses or meta-analyses. It has Gerl A, et al. Extragonadal germ cell tumors of the mediasti- been shownthatinpatientswithmalignant pericardial effusions, num and retroperitoneum: results from an international 87% had a prior history of malignancy . However, pericardial analysis. 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Approaching the On behalf of all authors, the corresponding author states that patient with an anterior mediastinal mass: a guide for clini- there is no conﬂict of interest. cians. J Thorac Oncol 2014;9:S102–9. Downloaded from https://academic.oup.com/omcr/article-abstract/2018/2/omx097/4898986 by Ed 'DeepDyve' Gillespie user on 16 March 2018 Pericardial effusion as an atypical initial presentation 57 9. Edoute Y, Ben-Arie Y. Primary malignant mediastinal germ mediastinum—a report of 15 cases. Eur J Radiol 2012;81: cell tumor causing pericardial effusion. Harefuah 1996;131: 1057–61. 88–9. 11. Dragoescu EA, Liu L. Pericardial ﬂuid cytology: an analysis 10. Li T, Li-Zhi L, Chun-Yan C, Wei-Dong Z, Ya-Ling K. CT ﬁnd- of 128 specimens over a 6-year period. Cancer Cytopathol ings of primary non-teratomatous germ cell tumors of the 2013;121:242–51. Downloaded from https://academic.oup.com/omcr/article-abstract/2018/2/omx097/4898986 by Ed 'DeepDyve' Gillespie user on 16 March 2018
Oxford Medical Case Reports – Oxford University Press
Published: Feb 1, 2018
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