From the Department of Pathology (SF), University of Illinois at Chicago, Chicago, Illinois; Associated Retinal Consultants (MTT, MKW), William Beaumont Hospital, Royal Oak, Michigan; the Department of Ophthalmology (ERO), Henry Ford Hospital, Detroit, Michigan; Children’s Hospital of Michigan (JMP), Detroit, Michigan; Ophthalmic Oncology Service (DHA), Memorial Sloan-Kettering Cancer Center, New York, New York; and the Departments of Biomedical Science, Ophthalmology, and Pathology (RF), the Oakland University William Beaumont School of Medicine, Rochester, Michigan.
Presented at a meeting of the Verhoeff-Zimmerman Society, April 28, 2008, Miami, Florida.
The authors have no financial or proprietary interest in the materials presented herein.
Address correspondence to Robert Folberg, MD, Departments of Biomedical Science, Ophthalmology, and Pathology, Oakland University William Beaumont School of Medicine, 2200 N. Squirrel Road, Rochester, MI 48309.
Teratomas are tumors that arise from more than one germ layer, usually from all three.1 Teratomas have been described to originate from the orbit,2 or to erode into it from the sinuses3 or the cranial fossa.4,5 Although orbital teratomas may erode into the eye and even destroy it, the eye is usually displaced anteriorly and may suffer from exposure.6 The medical literature contains only two previous reports of intraocular teratomas without concomitant orbital involvement.7,8 Neither of these reports describes the clinical characteristics of this unusual intraocular lesion. To the best of their knowledge, the authors provide the first clinicopathologic correlation of intraocular teratoma associated with a benign sacrococcygeal teratoma.
A large sacrococcygeal tumor was detected on routine ultrasonographic prenatal evaluation of a female fetus at 20 weeks’ gestation. The parents and two older siblings were healthy, and the pregnancy was uneventful. Except for retinoblastoma in the mother’s cousin, the family history was unremarkable.
The infant was delivered by planned cesarean section at 32 weeks’ gestation because of tumor growth. The infant weighed 3,118 g at birth (Fig. 1A). The sacrococcygeal lesion was removed 1 day after delivery. The lesion weighed 710 g and contained elements of all three germinal layers. The cells lacked atypia and pleomorphism, and no elements of yolk sac were identified. The tumor was diagnosed as a benign teratoma. The postoperative course was uneventful, and the infant was discharged from the hospital weighing 2,113 g.
Figure 1. (A) Newborn Infant with Sacrococcygeal Teratoma. (B) Fundus Image (retcam; Clarity Medical Systems, Pleasanton, CA) of the Two Lesions Identified at the First Ophthalmic Examination 4 Weeks After Birth. (C) Ultrasonogram of a Cystic Lesion of One of the Lesions Shown in Fig. 1B with Accompanying Retinal Detachment.
Four weeks after birth, the patient was referred for routine screening to exclude retinopathy of prematurity. Findings on complete eye examination were unremarkable except for two discrete exophytic chorioretinal lesions in the right eye (Fig. 1B) that did not disrupt the surface retinal vasculature. The lesions measured 4 and 8 disc diameters, respectively, along their greatest dimensions. Both lesions were peripapillary, one nasal and one temporal to the optic disc, and both lesions spared the macula. Ultrasound examination at that time showed two cystic subretinal masses (Fig. 1C), with no shadowing that could result from calcifications. At follow-up examination 4 weeks later, the retina was totally detached and the eye was considered blind by lack of pupillary response to light. Retinoblastoma was considered unlikely because of the clinical appearance of the masses and the cystic, noncalcified appearance on both ultrasonography and computed tomography.
Fourteen weeks after birth, the right eye was significantly larger than the left eye. A right afferent pupillary defect was present. The right cornea was cloudy, the anterior chamber was shallow, iris neovascularization was present, and the tumor appeared to fill the entire posterior segment. Eye movements remained unaffected. The right eye was enucleated because it was blind and it contained a growing undiagnosed tumor.
On gross examination, the right eye measured 17.5 × 20.0 × 17.5 mm. On transillumination, two shadows were identified, corresponding to the clinically described intraocular masses. The eye was opened horizontally in a pupil–optic nerve plane. The retina was completely detached, and a large cystic white lesion occupied two-thirds of the subretinal space (Figs. 2A and 2B).
Figure 2. (A) Gross Photograph of the Pupil–Optic Nerve Section. (B) Gross Photograph of the Superior Cap. (C–H) Photomicrographs of the Superior Cap Stained with Hematoxylin–Eosin. (C) Entire Section, Bar = 5 mm. (D) Brain Tissue, Original Magnification ×2, Bar = 500 μm. (E) Cartilage, Original Magnification ×10, Bar = 100 μm. (F) Muscle Fibers, Original Magnification ×20, Bar = 100 μm. (G) Mucinous Glands, Original Magnification ×10, Bar = 100 μm. (H) Respiratory Epithelium, Original Magnification ×10, Bar = 100 μm.
On routine light microscopy, elements of all three germinal layers were detected in the cystic mass beneath the detached retina (Fig. 2C), including brain tissue (Fig. 2D), cartilage (Fig. 2E), striated muscle (Fig. 2F), and gastrointestinal mucosa (Fig. 2G). The large subretinal cyst was lined with respiratory epithelium (Fig. 2H). Malignant tissue elements were not identified. A neovascular membrane lined the iris. The anterior chamber angle and the ciliary body were within normal limits.
The sacrococcygeal lesion contained elements of endodermal, ectodermal, and mesodermal tissues. No malignant germ cell tumor components were identified. Specifically, there were no elements of yolk sac neoplasia. Representative areas of the sacral lesion are shown in Figure 3, including primordial retinal and retinal pigment epithelial tissues (see Fig. 3C).
Figure 3. Photomicrographs of the Sacrococcygeal Lesion Stained with Hematoxylin–Eosin. (A) Entire Section, Bar = 1 mm. (B) Different Tissues Within the Lesion, Original Magnification ×1, Bar = 500 μm. (C) Forming Optic Cup (primordial Retinal Tissue) Within the Sacral Teratoma, Original Magnification ×5, Bar = 100 μm.
To the best of the authors’ knowledge, this is the first clinicopathologic description of the clinical course of an intraocular teratoma from birth to enucleation of an eye filled with tumor. The only external manifestation of the intraocular lesion in the current patient was enlargement of the eye. In the two previously reported cases of intraocular teratoma, the eye was reported to be severely distorted at birth.7,8 The eye was enlarged in one case7 and microphthalmic in the other.8
The intraocular lesion in the current patient grew to fill the eye during the 12 weeks of follow-up and observation. The lesional growth rate was faster than expected for retinoblastoma. Moreover, the clinical characteristics of the tumor—the clinical appearance and the cystic architecture detected by ultrasonography and computed tomography—were inconsistent with the diagnosis of retinoblastoma. Internal calcifications that were not present in this case are typical for retinoblastoma,9,10 but also could have appeared within a teratoma; thus, these findings would not have assisted in the differential diagnosis. The growth rate of the lesion in the current patient was slower than the growth noted in the two previous cases of intraocular teratoma (even when adjusted for the degree of prematurity of the patient) because in each of these two previously reported cases, the lesions filled the eyes by birth.
Tissues found within the intraocular mass were derived from ectoderm (brain), mesoderm (cartilage and muscle), and endoderm (respiratory epithelium). In this respect, the current case is similar to the previous reports.7,8 Because there was no sign of malignancy of the sacrococcygeal tumor, the intraocular tumor was not a metastasis but a second primary teratoma in this patient.
New information about the cellular origin of extragonadal germ cell tumors and teratomas indicates that they are derived from precursor cells that have undergone at least some degree of “erasement” or re-establishment of genomic imprinting (a typical feature of germ cells), strongly suggesting that all germ cell tumors and teratomas are derived from germ cells.11 Migration of primitive germ cells is still the best explanation of the distribution of human germ cell tumors along the midline of the body.11 Germ cells migrating to the area of the orbit are believed to give rise to orbital teratomas.6 Kivela et al.7 hypothesized that intraocular teratomas originate through entrapment of germ cells within the eye by the invaginating optic cup. The development of a sacrococcygeal teratoma and an intraocular teratoma in the same patient suggests that migration of cells caudally down the midline explains the origin of both teratomas in the current patient.
- Howes ELJ, Rao NA. Basic mechanisms in pathology. In: Spencer WH, Eagle RCJ, Folberg R, , eds. Ophthalmic Pathology: An Atlas and Textbook, 4th ed., vol. 4. Philadelphia: Saunders; 1996:3020.
- Chang DF, Dallow RL, Walton DS. Congenital orbital teratoma: report of a case with visual preservation. J Pediatric Ophthalmol Strabismus. 1980;17:88–95.
- Weiss AH, Greenwald MJ, Margo CE, et al. Primary and secondary orbital teratomas. J Pediatr Ophthalmol Strabismus. 1989;26:44–49.
- Prause JU, Borgesen SE, Carstensen H, et al. Cranio-orbital teratoma. Acta Ophthalmol Scand Suppl. 1996;219:53–56. doi:10.1111/j.1600-0420.1996.tb00388.x [CrossRef]
- Tobias S, Valarezo J, Meir K, et al. Giant cavernous sinus teratoma: a clinical example of a rare entity. Case report. Neurosurgery. 2001;48:1367–1370. doi:10.1097/00006123-200106000-00041 [CrossRef]
- Kivela T, Tarkkanen A. Orbital germ cell tumors revisited: a clinicopathological approach to classification. Surv Ophthalmol. 1994;38:541–554. doi:10.1016/0039-6257(94)90147-3 [CrossRef]
- Kivela T, Merenmies L, Ilveskoski I, et al. Congenital intraocular teratoma. Ophthalmology. 1993;100:782–791.
- Leventer DB, Corona J, Linberg JV, et al. Congenital intraocular teratoma associated with eyelid coloboma. Am J Ophthalmol. 2001;132:277–279. doi:10.1016/S0002-9394(01)00827-3 [CrossRef]
- Bullock JD, Campbell RJ, Waller RR. Calcification in retinoblastoma. Invest Ophthalmol Vis Sci. 1977;16:252–255.
- Roth DB, Scott IU, Murray TG, et al. Echography of retinoblastoma: histopathologic correlation and serial evaluation after globe-conserving radiotherapy or chemotherapy. J Pediatr Ophthalmol Strabismus. 2001;38:136–143.
- Oosterhuis JW, Stoop H, Honecker F, et al. Why human extragonadal germ cell tumours occur in the midline of the body: old concepts, new perspectives. Int J Androl. 2007;30:256–263. doi:10.1111/j.1365-2605.2007.00793.x [CrossRef]