Yolk sac tumor (endodermal sinus tumor) is rarely encountered in the temporal bone. Facial nerve paralysis can be a primary manifestation of this condition. Histologically, the tumor can be difficult to diagnose, although elevated levels of alpha fetoprotein can facilitate its identification.
In this report, we describe the case of an 18-month-old girl who developed peripheral VIIth nerve palsy and a polypoid mass in the left external ear canal 3 months following myringotomy. Computed tomography and magnetic resonance imaging revealed that the tumor involved the left external ear canal, middle ear space, and mastoid air cells. Biopsies were consistent with a yolk sac tumor. Special staining demonstrated that only a very few tumor cells were positive for alpha fetoprotein, despite the markedly elevated level of alpha fetoprotein in her serum. The patient was treated with chemotherapy, which included cisplatin, etoposide, and bleomycin. Within a period of weeks, she experienced a complete reversal of her left VIIth nerve palsy, a marked decrease in her serum alpha fetoprotein levels, and a dramatic resolution of the tumor as demonstrated radiographically. Such a successful chemotherapeutic response in this case argues against surgical intervention in other cases, particularly in view of the risk of serious complications with surgery.
Yolk sac tumor (endodermal sinus tumor) of the head and neck region is extremely rare.  In the English-language literature, only two cases of yolk sac tumor of the temporal bone have been described.  In this report, we present a rare case of an 18-month girl with a rapidly progressive and extensive yolk sac tumor. This patient presented with bilateral otitis media with effusions, which necessitated bilateral myringotomies and placement of pressure-equalizing tubes. Three months later, she returned with an enlarged left aural polyp and ipsilateral facial nerve palsy. The rapid growth of the tumor required multiple biopsies for histopathologic confirmation. Markedly elevated serum alpha fetoprotein levels facilitated the diagnosis. A dramatic response to chemotherapy, which included a complete resolution of the facial nerve paralysis, was subsequently observed. In this article, we report the morphologic features of the tumor and review the investigative procedures.
The patient was born to a 26-year-old mother in October 1994. There were no complications during the pregnancy and delivery. During her first year of life, the patient developed recurrent bilateral otitis media. In December 1995, she underwent bilateral myringotomies and placement of pressure-equalizing tubes. Serous effusions, but no other abnormalities, were noted at this time.
In March 1996, the patient was taken to the emergency room with left peripheral VIIth nerve palsy and left otorrhea. The paresis failed to improve after treatment with antibiotics and steroids. Physical examination revealed a large polyp in the left external auditory canal (figure 1A), cloudy left otorrhea, and a left peripheral VIIth nerve palsy (figure 1B). Biopsies from the mass were suspicious but inconclusive for malignancy.
Computed tomography (CT) without contrast of the temporal bone revealed that a soft tissue mass filled the left external auditory canal, middle ear space, and mastoid air cells. Although the ossicular chain was intact, there was some dehiscence of the external auditory canal, which suggested a confluence of the mass with the parotid gland. Magnetic resonance imaging (MRI) of the head revealed the presence of a large mass that involved the entire left temporal bone and extended to the left cerebellopontine angle cistern (figure 2). No abnormal vasculature was noted.
The patient failed to improve on antibiotics. Laboratory studies revealed that her serum alpha fetoprotein level was 7,020 ng/ml (normal: 0-10). Her serum chemistry panel, liver function test, coagulation profile, urinalysis, and beta human chorionic gonadotropin and carcinoembryonic antigen levels were well within normal limits. CT studies of the chest, abdomen, and pelvis were normal, and a technetium bone scan showed increased uptake only in the area of the left temporal bone. Bone marrow aspirate and cerebrospinal fluid studies also were negative. The patient was taken to the operating room in April 1996 for further biopsies and debulking of the lesion, which by that time had grown to fill the entire left external auditory canal.
The biopsy specimen consisted of several fragments of tan to red tissue and measured 1.1 x 0.5 x 0.4 cm in aggregate. Sections from the tumor were fixed in 10% buffered formalin and in B-5 fixative. The tissue was processed routinely, and paraffin-embedded sections were stained with hematoxylin and eosin for immunohistochemical studies. A Ventana automatic stainer was used for the immunohistochemical studies. The antibodies used and the results of the staining are listed in the table. Tissue for ultrastructural examination was fixed in glutaraldehyde. The tissue was osmicated, dehydrated in ethanol, and embedded in epoxy resin in the conventional manner. Sections were examined with a Phillips-Zeiss transmission electron microscope.
Microscopic examination showed that a mixed glandular and sheet-like arrangement of tumor had infiltrated the dermis and soft tissue of the external ear canal. The tumor cells contained vacuolated cytoplasm and a single large vesicular nucleus. Small eosinophilic hyaline globules were noted in the cytoplasm. In one area, the tumor cells were arranged around a central blood vessel, which was surrounded by a space lined with tumor cells, which formed a Schiller-Duval body (figure 3). Periodic acid-Schiff (PAS)-stained sections showed numerous PAS-positive hyaline cytoplasmic bodies. Mitotic figures were numerous. The tumor cells showed a strong positivity for cytokeratin and vimentin. Desmin, S-100 protein, chromogranin, synaptophysin, somatostatin, and factor VIII showed negative staining within tumor cells. Only a very few tumor cells showed strong alpha fetoprotein positivity.
On electron microscopy, the tumor cells contained abundant cytoplasm, irregular nuclei, and a single prominent nucleolus. The cells showed apical microvilli and were connected by well-developed junctional complexes. The tumor cell cytoplasm contained scattered mitochondria, profiles of rough endoplasmic reticulum, Golgi's apparatus, and a few nonspecific intermediate filaments and particulate glycogen (figure 4).
The patient was started on chemotherapy with cisplatin, etoposide, and bleomycin. The tumor responded dramatically (figure 5). Clinically, the patient experienced a complete resolution of her facial nerve palsy (figure 6), and her serum alpha fetoprotein levels returned to normal (4.6 ng/ml). Followup CT and MRI studies revealed a dramatic regression of the tumor (figure 7). In total, the patient received ten cycles of chemotherapy.
At the time this paper was finalized, the patient had been followed for more than 36 months since her last treatment. Her serum alpha fetoprotein level was 2.4 ng/ml, and she was doing well.
Yolk sac tumor is the most common malignant germ tumor found in infants. The sacrococcygeal area is the most common site of involvement in both newborns and infants.  In older children, the primary locations are the ovaries and the testes. [5,6] Less common primary sites include the pineal glands, third ventricle, anterior mediastinum, vagina, vulva, retroperitoneum, diaphragm, liver, and orbit. [2,7-9]
Primary yolk sac tumor rarely occurs in the temporal bone. [1-3] In the case presented here, a large and locally invasive mass was discovered occupying the left temporal bone, eroding the mastoid cortex, extending into the parotid gland, and involving the skull base. The diagnosis of yolk sac tumor was reached after a careful evaluation of the clinical presentation as well as the microscopic findings. The determinant points were the elevated serum alpha fetoprotein level, the histology of the tumor, and the dramatic response to triple-drug chemotherapy. Although mildly elevated serum alpha fetoprotein levels can be encountered in nonneoplastic conditions such as cirrhosis, hepatitis, and pregnancy, neoplasms that arise in the liver and germ cells (as well as the pancreas and stomach on rare occasions) can result in tremendously high elevations. Following adequate resection of these tumors, the serum alpha fetoprotein level drops rapidly, thus making it a sensitive marker of response to therapy. As seen in thi s case, histologic staining for alpha fetoprotein in these tumor cells is not 100% sensitive; in fact, alpha fetoprotein negativity in yolk sac tumors has been reported in 7% of tumors in the pediatric age groups. 
The differential diagnoses of a mass lesion of the temporal bone in pediatric age groups include rhabdomyosarcoma, congenital cholesteatoma, lymphoma, hemangioma, teratoma, meningocele, dermoid cyst, undifferentiated carcinoma, and endolymphatic sac tumors. The endolymphatic sac, located between the dura and the posterior surface of the petrous portion of the temporal bone, originates in the neuroectoderm and is lined with both columnar and simple cuboidal epithelium. Tumors that arise from the endolymphatic sac tend to be low-grade adenocarcinomas; a few cases are associated with von Hippel-Lindau disease." [11-13] A papillary variant of this tumor occurs predominantly in women, and takes on a more aggressive clinical course. [14-15] These tumors are positive by S-100 protein and negative for alpha fetoprotein. None of these tumors has been associated with elevated serum alpha fetoprotein levels. Glomus tumors (paragangliomas), the most common neoplasms arising from the middle ear, should also be considered in the differential diagnosis. [16-18] Microscopically, the tumor is highly vascular and divided by nests or "cell balls" composed of large ovoid-shaped cells with amphophilic cytoplasm. Immunohistochemically, the paraganglioma cells are reactive for catecholamines, neuron-specific enolase, chromogranin, and synaptophysin. Ultrastructurally, the cells contain numerous dense-core granules of the neurosecretory type.
Histologically, the yolk sac tumor can be difficult to diagnose, as exemplified by the need to repeatedly perform biopsies in our patient. This tumor has different histologic patterns: typical (reticular, solid, papillary, parietal), polyvesicular, hepatoid, glandular, and mixed.  In our patient, the tumor cells were arranged in a mixed pattern of solid-sheet and glandular formation with indistinct lumina. The tumor cells had a single vesicular nucleus and vacuolated cytoplasm. PAS-positive hyaline globules were identified in the cytoplasm of several cells. Schiller-Duval bodies were present. The tumor cells were strongly positive for cytokeratin and vimentin. S-100 protein, chromogranin, synaptophysin, and desmin were all negative. Although only a very few tumor cells were positive for alpha fetoprotein, the serum alpha fetoprotein level was markedly elevated.
To our knowledge, this is only the third reported case of a yolk sac tumor that involved the temporal bone. Given the rarity of this tumor in this location, no definitive treatment has been established. [2,3] A combination of surgical excision and chemotherapy has been the mainstay of treatment for ovarian yolk sac tumors.  However, in the temporal bone, where critical structures such as the facial nerve and internal carotid artery are involved, surgical excision might not be a feasible option. The role of radiation therapy has not been clearly established. Radiation might have an adjunctive role when it is selectively applied, but it must be administered with extreme caution in the pediatric age group. In our patient, the dramatic and favorable response to triple-drug chemotherapy has deferred the need for additional treatment. A similar response to chemotherapy was noted in the two previously reported cases of yolk sac tumor of the temporal bone. 
From the Department of Surgery, Division of Otolaryngology (Dr. Frank and Dr. Anand), and the Department of Pathology (Dr. Subramony), University of Mississippi Medical Center, Jackson.
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