Primitive Neuroectodermal Tumorof the HeartNnamdi Nwaejike, MD, Doris Rassl, FRCPath,Hugo Ford, MD, and Stephen R. Large, FRCS
Departments of Cardiothoracic Surgery, Histopathology, andOncology, Papworth Hospital, Cambridge, United Kingdom
We present a case of primitive neuroectodermal tumor ofthe left atrium with involvement of the coronary sinus.The initial presentation was of cardiac tamponade result-ing from the size of the tumor. There was no evidence oftumor elsewhere, and after complete resection and with-out adjuvant chemotherapy the patient is well at 2-yearfollow-up. There has been no evidence of tumor recur-rence. This is a rare reported case of resection of a cardiacprimitive neuroectodermal tumor without adjuvant che-motherapy. Other cases in the literature have beentreated by orthoptic transplantation and resection withchemotherapy.
(Ann Thorac Surg 2012;93:e27–9)© 2012 by The Society of Thoracic Surgeons
Primary cardiac tumors are rare; the incidence rangesfrom 0.001% to 0.28%. Malignant tumors account for
25% of primary cardiac tumors [1]. Primary primitiveneuroectodermal tumor (PNET) derives from carcino-genic alteration of pluripotent neural crest cells andrarely presents as an organ-based neoplasm [2]. Wepresent a rare case of primary PNET of the heart.
A 42-year-old woman presented with a 6-week history ofprogressively worsening breathlessness, abdominal dis-tention, and peripheral edema. Eighteen weeks earliershe had delivered a healthy baby by cesarean section.She had had 3 previous pregnancies (1 termination ofpregnancy, 1 miscarriage, and 1 cesarean section). Shewas taking sertraline 100 mg (Zoloft) for postnatal de-pression and lansoprazole 15 mg (Prevacid) for gastro-esophageal reflux disease. She gave up smoking in 1993(10 pack years smoking history) and her mother hadbreast cancer at age 40 years. There was no other historyof malignancy in her immediate family. Echocardiogra-phy demonstrated a 7 cm � 8 cm mass behind the heart,a large pericardial effusion, and good left ventricularfunction. Two liters of blood-stained pericardial fluidwere drained by pericardiocentesis. The exudate had aprotein content of 36 g/dL and cytologic examinationrevealed mesothelial cells and no malignant cells. Car-diac magnetic resonance imaging confirmed a 7 cm � 8cm mass adherent to the posterior wall of the heart.There was obstruction of the inferior vena cava (Fig 1).Whole-body computed tomography showed no tumorelsewhere. This solid seemingly encapsulated mass wasadherent to the first 2 cm of the coronary sinus andappeared to arise from the posterior free wall of the leftatrium.
Cardiopulmonary bypass was achieved by ascendingaortic arterial return and superior vena cava and right
Accepted for publication Aug 15, 2011.
Address correspondence to Dr Large, Department of Cardiothoracic
Surgery, Papworth Hospital, Papworth Everard, Cambridge CB38RE,United Kingdom; e-mail: [email protected].© 2012 by The Society of Thoracic SurgeonsPublished by Elsevier Inc
femoral venous drainage. With appropriate cardiac pro-tection the inferior vena cava was clamped and discon-nected, and division of the right superior and inferiorpulmonary vein pair afforded good access to the poste-rior aspect of the heart. A vascular, nonhomogeneousmass was seen to be densely adherent to the posteriorwall of the left atrium and the coronary sinus. It was notattached to the pericardium nor was there any macro-scopic evidence of pericardial or epicardial involvement.Satisfactory clearance of the tumor was achieved. Thecoronary sinus was reconstructed with an oval patch ofbovine pericardium (6 cm � 2cm) using 5-0 polypropyl-ene, as was the left atrium (4 cm � 4 cm square bovinepericardial patch) (Supple Peri-Guard, Bio-Vascular, Inc,Saint Paul, MN). The final tumor clearance was satisfac-tory and the inferior vena cava and right pulmonary veinpair were reattached. The pericardial space was washedout with water in an attempt to remove any remainingmalignant cells. The patient made an uneventful recov-ery and was discharged on the sixth postoperative day foroncologic review. A postoperative magnetic resonanceimage confirmed tumor clearance and no evidence oftumor involvement elsewhere (Fig 2).
The tumor infiltrated the myocardium and was com-posed of solid sheets of atypical cells with vesicularnuclei, variably visible small nucleoli, and eosinophiliccytoplasm. Mitoses were seen and there was focal tumornecrosis. An associated brisk lymphocytic infiltrate waspresent in places. No evidence of gland formation, mucinproduction, or keratinization was apparent. Immuno-staining revealed the tumor to be focally positive forpancytokeratin (MNF116) (Fig 3), and diffuse staining forvimentin was also present. Positive staining was appar-ent for the neuroendocrine marker PGP9.5 (Fig 4) andfocally for synaptophysin, but other stains for neuroen-docrine differentiation, including chromogranin, neuron-specific enolase (NSE), and CD56 appeared negative. Thetumor was also negative for lymphoid markers (leuko-cyte common antigen [LCA], CD3, CD20, CD79a, CD30,CD15), BCL-2, CD1a, endothelial markers (CD31, CD34,von Willebrand factor [VWF]), estrogen receptor, smoothmuscle actin, epithelial membrane antigen, TTF-1, otherepithelial markers (AE1/AE3, BerEP4, AUA1, CK5/6,CK7, and CK20), mesothelial markers (calretinin, WT1),melanocyte markers (S100 and HMB45), and germ cellmarkers (human chorionic gonadotropin [HCG], placen-tal alkaline phosphatase [PLAP], �-fetoprotein [AFP]).
Fig 1. Cardiac magnetic resonance image showing the mass com-pressing the posterior heart wall.
CD68 stained infiltrating macrophages, but the tumor
0003-4975/$36.00doi:10.1016/j.athoracsur.2011.08.039
i
sna(
haweacsw
e28 CASE REPORT NWAEJIKE ET AL Ann Thorac SurgPRIMITIVE NEUROECTODERMAL TUMOR OF THE HEART 2012;93:e27–9
cells did not stain. Further immunostaining revealedvariable positivity for CD99.
In view of the immunoprofile, including variable pos-itivity for CD99, the possibility of a primitive neuroecto-dermal tumor was considered and a block of formalin-fixed paraffin-embedded tumor tissue was sent forcytogenetic analysis to Great Ormond Street Hospital.This revealed an EWSR1 rearrangement on fluorescencen situ hybridization analysis, and an EWS-FLII type II
transcript was detected by real-time polymerase chainreaction analysis, findings consistent with a diagnosis ofPNET. Analysis for the SS18 rearrangement was negative,excluding synovial sarcoma.
Comment
We present a case of primary PNET of the heart success-fully treated by resection alone.
After surgical resection the patient was free of recur-rence after a 2-year surveillance and remains so to date.Tumor has never been found elsewhere and we proposethat this represents a primary PNET of the left atrial freewall with involvement of the coronary sinus.
Fig 2. Postoperative cardiac magnetic resonance image showing ap-pearance after resection of mass.
rFig 3. Slides stained with MNF116. (Original magnification � 100.)
Primary cardiac tumors are rare; the incidence rangesfrom 0.001% to 0.28%. Malignant tumors account for 25%of primary cardiac tumors [1]. The most frequent primarymalignant cardiac tumors are angiosarcomas.
Primitive neuroectodermal tumor derives from carci-nogenic alteration of pluripotent neural crest cellsthrough a balanced reciprocal translocation t(11;22)(q24;q12) [2]. It rarely presents as an organ-based neoplasmand is typically seen in the soft tissues of the chest walland paraspinal region [2]. There is no clear guidance onthe treatment of PNET of the heart and we could findonly 1 other report of successful resection of the primarytumor with no adjuvant therapy [3]. Other managementoutcomes include 1 unresectable tumor [2], 1 case oftreatment by chemotherapy [4], and 2 cases of treatmentby orthoptic transplantation [5, 6].
We acknowledge the possibility that this could be acardiac metastasis behaving like a primary lesion be-cause primary tumors can undergo spontaneous regres-sion after treatment of metastases [7]. In a 10-year-periodreview of 18,751 postmortem examinations, Bussani andassociates [1] discovered 7,289 cases (39%) of previouslyundiagnosed malignant neoplasm. Six hundred andtwenty-two of these showed evidence of cardiac metas-tasis (9.1% of malignant tumors). However the heart wasfound to be the only target of metastasis in 10 cases(10/7,289 � 0.14%). The highest rates of cardiac metasta-es are seen from pleural mesothelioma (48.4%), mela-oma (27.8%), lung adenocarcinoma (21%), undifferenti-ted carcinoma (19.5%), lung squamous cell carcinoma18.2%), and breast carcinoma (15.5%) [1].
In our patient, 2-year follow-up with oncologic reviewas shown no evidence of recurrence of local tumor or oflate primary tumor. Follow-up was initially every 6eeks then every 6 months, and considering the side
ffects of adjuvant chemotherapy on her young familynd the complete surgical resection, it was decided toonsider adjuvant chemotherapy only if there were anyigns of recurrence. We thus conclude that this tumoras a primary PNET of the heart successfully treated by
Fig 4. Slides stained with PGP9.5. (Original magnification � 50.)
esection alone.
e29Ann Thorac Surg CASE REPORT NWAEJIKE ET AL2012;93:e27–9 PRIMITIVE NEUROECTODERMAL TUMOR OF THE HEART
References
1. Bussani R, De-Giorgio F, Abbate A, Silvestri F. Cardiacmetastases. J Clin Pathol 2007;60:27–34.
2. Besirli K, Arslan C, Tuzun H, Oz B. The primitive neuroecto-dermal tumor of the heart. Eur J Cardiothorac Surg 2000;18:619–21.
3. Kath R, Krack A, Schneider C, Katenkamp D, Hoffken K.Cardiac manifestations of peripheral primitive neuroectoder-mal tumor (pPNET): a rare case. Dtsch Med Wochenschr2000;125:1192–4.
4. Rajappa S, Gundeti S, Varadpande L, Bethune N, Rao S,Digumarti R. Cardiac primitive neuroectodermal tumor pre-
senting as acute coronary syndrome. J Clin Oncol2007;25:449–51.
5. Charney DA, Charney JM, Ghali VS, Teplitz C. Primitiveneuroectodermal tumor of the myocardium: a case report,review of the literature, immunohistochemical, and ultra-structural study. Hum Pathol 1996;27:1365–9.
6. Chai Y, Huang L, Yue L. Peripheral primitive neuroectoder-mal tumour of left ventricular wall origin: a rare case. ActaCardiol 2007;62:523–4.
7. Fairlamb DJ. Spontaneous regression of metastases of renalcancer: a report of two cases including the first recorded
regression following irradiation of a dominant metastasis andreview of the world literature. Cancer 1981;47:2102–6.Recommended
