Intrapericardial Yolk Sac Tumor in an Infant Girl

EDWARD NELSON, MD, AND PETER STENZEL, MD, PHD

This article is a report on the first known case of an intrapericardial yolk sac (endodermal sinus) tumor discovered in a 14-month-old girl. The patient presented with a systolic murmur, cardiomegaly, and manifestations of cardiac failure. At surgery a large, friable, intrapericardial mass with no evidence of extrapericardial spread was found. Histologic and immunohistochemical findings were diagnostic of yolk sac tumor. Following initial resection, chemotherapy, and a second resection 13 months after the first, the patient died 24 months after diagnosis. Tumor enlargement was associated with elevated serum alpha-fetoprotein levels.

Cancer 60:1567-1569. 1987.

INCE TEILUM'S IDENTIFICATION Of endodermal S sinus tumors as gonadal germ cell neoplasms,' tumors with the same characteristic histologic patterns have been found in extragonadal primary sites where they also have been designated yolk sac tumors (YST). Many of these sites are midline and include the sacro- coccygeal region, the anterior mediastinum, the pineal region, and the infant Primary YST have also been reported in the stomach,6 liver,' vulva,8 retroperi- toneurn,','' prostate,'' and face.'* We report a case of an intrapericardial YST in an infant girl. Although one in- trathoracic YST in a female patient,13 has been reported, we are aware of no previously reported intrapericar- dial YST.

Case Report

A 14-month-old Caucasian girl was admitted to the Oregon Health Sciences University in Portland with increasing imta- bility, pallor, and abdominal distention. She was born after an uncomplicated term pregnancy. The neonatal period was re- markable only for the discovery of a systolic heart murmur. Persistence of the murmur and electrocardiographic evidence of right ventricular hypertrophy suggested an atrial septa1 de- fect. Physical examination upon admission revealed limpness, pallor, hepatosplenomegaly, and a systolic heart murmur. Roentgenograms of the chest showed cardiomegaly. Echocar- diography showed a large, mobile mass attached to the pericar- dium anterior and superior to the base of the heart. Thoracot- omy on the day of admission revealed 150 ml of bloody peri- cardial fluid and a friable 4-X-6-X-8-cm mass located completely within the pencardial space and attached to the

From the Department of Pathology, Oregon Health Sciences Uni- versity School of Medicine, Portland, Oregon.

Address for reprints: Peter Stenzel, MD, PHD, Department of Pa- thology, UHS- 19. Oregon Health Sciences University, 3 18 l S.W. Sam Jackson Park Road. Portland, OR 9720 I .

Accepted for publication April 7, 1987.

aorta and pulmonary artery. Frozen sections were interpreted as a poorly differentiated malignant tumor. As much tumor as could be safely resected was removed. Permanent sections demonstrated yolk sac tumor without evidence of other differ- entiation. Metastases were not evident. Serum alpha-fetopro- tein (AFP) was not elevated on the second day after surgery.

Various antineoplastic chemotherapeutic regimens were ad- ministered over the next 19 months including: vinblastine, bleomycin, cisplatinurn, doxorubicin, cyclosphosphamide, ac- tinomycin D, and methotrexate. Elevated serum AFP levels (2500 ng/ml) were first noted 1 1 months after the initial tumor resection. Two months later, radiographs showed evidence of recurrence. A second thoracotomy 13 months after the first revealed friable, edematous tumor involving the arch of the aorta, pulmonary artery, and innominate vein as well as the left phrenic and vagus nerves. The histologic appearance was identical to the initial specimen. Radiation therapy was given and chemotherapy continued. Superior vena cava compres- sion and elevated serum AFP levels were noted after treat- ment. The patient died 24 months after diagnosis without clinical evidence of tumor in any site except the pericardium and environs. No autopsy was performed.

Pathologic Findings

All sections contained extensive areas of reticular pat- tern composed of large cells and variably sized spaces, which appeared as intracytoplasmic vacuoles or as spaces surrounded by cytoplasmic extensions of a few cells. More solid collections of cells were arranged within the reticular areas in a somewhat regular lattice fashion and merged at their borders with the reticular formations (Fig. 1). The solid structures often contained prominent thin-walled vessels in their centers. There were scattered duct-like structures often invested by concentrically arranged dense fibrous tissue and lined by a single layer of cuboid cells (Fig. 2). These frequently contained apically placed, PAS-positive, diastase-resis-

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1568 CANCER October I 1987 Vol. 60

FIG. 1 . Yolk sac tumor composed ofarray ofreticular areas and solid areas (H & E X75).

tant granules, Fibrous bands irregularly divided the tumor. The ducts were frequently in the fibrous septa or at the edges of the solid structures. Intracellular and extracellular PAS-positive, diastase-resistant hyaline globules were focally prominent (Fig. 3).

Immunohistochemical staining for AFP was done with rabbit anti-human AFP antiserum (Dako Corp., Santa Barbara, California) by the avidin-biotin-peroxi- dase complex technique. Staining was present in most cells and was intense in the reticular areas.

Discussion

The histologic appearance of the tumor conforms to the reticular, microcystic, solid, and mesenchymal pat- terns described by Teilum.’ Typical endodermal sinus

FIG. 2. A tubular structure invested by dense connective tissue re- sembles an interlobular bile duct (H & E X315).

FIG. 3. Abundant hyaline globules in a reticular area (H & E X375).

structures with mantling of vessels by a single layer of epithelium were not conspicuous. We believe, however, that the characteristic pattern of most areas, the hyaline bodies, the paucity of necrosis, the failure to identify syncytiotrophoblasts, the tumor AFP immunoreactiv- ity, and the elevated serum AFP levels clearly indicate that this case represents a YST. The intrapericardial lo- cation of the tumor was established at surgery when extrapericardial extension was sought and excluded. Ev- idence of another site of involvement in this patient was also repeatedly sought and not found. Thus, we submit that this case represents a primary intrapericardial YST in an infant girl and that it may be the first reported case of a YST in that exact location. An intrapericardial ma- lignant teratoma has been reported.14 A mediastinal, ex- trapericardial YST in an infant girl was recently re- ported.13 However, primary malignant germ cell tumors of the mediastinum are extremely rare among females.’’

Extragonadal germ cell tumors invariably occur at sites where teratomas are known to occur. The usual median sites of germ cell tumors and teratomas have been attributed to the near midline migratory route of of germ cells from the yolk sac to the genital ridge^.^ It has been suggested that ovarian teratomas are derived from germ cells that have undergone the first meiotic division, while extragonadal teratomas arise from premeiotic germ cells.16

YST derives its name from the strikingly similar mi- croscopic appearance of the tumor to yolk sac struc- tures” and presumably arises from germ cell-derived tissue differentiating along this line. Normal yolk sac and some regions of YSTs have a common tendency toward hepatic differentiation. The constant association between AFP production and YST hi~tology,~ and the production of AFP by a normal embryologic yolk sac

No. 7 INTRAPERICARDIAL YOLK SAC TUMOR - Nelson and Stenzel 1569

and developing liver, as well as some hepatic neoplasms provides further biochemical evidence for this common development. The hepatic anlage appears as a diverticu- lum of the yolk sac on the 18th day in the 7-somite embryo.I8 Thus, not only does the yolk sac perform a rudimentary hepatic function in the embryo (AFP pro- duction), but the liver is, in a sense, derived from the yolk sac.

Hepatic differentiation within YST has been sug- gested by the occurrence of cells resembling hepato- cytes. Similar hepatocyte-like cells have been observed in other neoplasms with elevated AFP, including an ovarian Sertoli-Leydig cell tumor,20 a case of the newly described diffuse embryoma of the testis,21 and a pri- mary mediastinal tumor of undetermined origin in a 25-year-old man with a microscopic appearance resem- bling hepatoblastoma.22 Ducts have been identified in some of these tumors that have hepatoid differentiation. Similar structures have been noted in early descriptions of YST and in some accounts of h e p a t o b l a ~ t o m a . ~ ~ . ~ ~ Other epithelial structures have been observed in ovar- ian YST, but were interpreted as intestinal differentia- tion.2s We suggest that the duct-like structures in the current case are by their morphology reminiscent of bile ducts.

Despite some apparent inroads with aggressive multi- agent chemotherapy, the prognosis of extragonadal, nonseminomatous germ cell tumors remains poor. The apparent absence of metastatic spread in this case, de- spite local aggressive growth, is remarkable and may perhaps be attributed to the chemotherapeutic regimens in what was only a partially resectable primary lesion. Yolk sac tumor may be added to the differential diag- nosis of intrapericardial masses.26 Such a diagnosis might be supported or tested by serum AFP determina- tion. We cannot explain our patient's lack of serum AFP elevation on the second day after surgery. Rapid clear- ance seems unlikely since the serum half-time of AFP may be expected to be at least 3 days.27

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