| Abstract|| |
We report a case of pure orbital yolk sac tumor (YST) in an 11-month-old infant, which is a rare entity. The child presented with progressive painless swelling of the right eye and on examination had proptosis, chemosis, and lid edema. Systemic examination was within normal limits. Magnetic resonance imaging (MRI) orbit revealed a lobulated heterogeneously enhancing right retroocular mass extending up to the orbital apex, displacing the optic nerve and eroding the medial orbital wall. Biopsy of the lesion revealed pure YST histology. Serum alpha-fetoprotein (AFP) was markedly raised at 76900 ng/mL. She was started on infant bleomycin etoposide cisplatin (BEP) chemotherapy protocol. There was a good clinical and radiological response. A high index of malignancy is required in young children presenting with orbital proptosis. A multidisciplinary approach and early intervention are essential to save both vision and life.
Keywords: Germ cell tumor, infant, malignancy, orbit
|How to cite this article:|
Mishra V, Jain S, Malhotra P, Durga G, Kapoor G. Primary orbital yolk sac tumor in an infant: A rare entity. Indian J Pathol Microbiol 2023;66:652-4
| Introduction|| |
Incidence of germ cell tumors (GCT) has two distinct peaks in children, first in 0–4 years and second during pubertal spurt in adolescents. Malignant GCT account for about 3% of all malignancies in children aged 0–18 years and nearly 15% of cancers in adolescents. GCT usually arise from gonads (ovary and testes). Extragonadal GCT of the head and neck comprise only 5% of all benign and malignant GCT. Orbit is an uncommon site for the occurrence of extragonadal GCT. Usually, these are teratomas; however, pure yolk sac tumors (YST) are rare (20% of all cases). Owing to its rarity, no proper universal treatment protocol is available for this entity. Here we report a case of an orbital YST in an 11-month-old girl. In this study, we present a review of various differentials of orbital tumors in children along with a brief review of the presentation, diagnosis, and management of orbital YST in children.
| Case Report|| |
An 11-month-old girl presented with progressive painless swelling of the right eye for 15 days. There was no history of fever or trauma. On examination, she had proptosis and chemosis of the right eye with lid edema [Figure 1]. Eye movements and pupillary reflexes could not be elicited. There was no evidence of optic nerve atrophy or papilledema. The left eye was normal. She had no palpable lymphadenopathy. The systemic examination was unremarkable. Magnetic resonance imaging (MRI) of the orbit revealed the tumor to be extraocular [Figure 1]. On histopathological examination, the neoplasm was composed of cells arranged in microcystic, reticular, papillary, and glandular configuration. The cells were cuboidal to columnar with pleomorphic and hyperchromatic nuclei. Extracellular hyaline globules were noted. The microcysts were filled with myxoid material and mitosis was readily seen. No necrosis was evident. These findings were suggestive of GCT.
|Figure 1: (1) Pre-treatment: Axial proptosis with chemosis and lid edema. (2) MRI orbit: Lobulated heterogeneously enhancing right retroocular mass extending up to the orbital apex. The optic nerve was displaced superiorly by the lesion along with mild erosion of the adjacent medial wall. (3) Clinical response to neoadjuvant chemotherapy. (4) Good radiologic response to chemotherapy|
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On immunohistochemistry (IHC), tumor cells expressed cytokeratin, SALL4, and Glypican 3 that were negative for Epithelial Membrane Antigen (EMA)[Figure 2]. Serum alpha-fetoprotein (AFP) was 76900 ng/mL and beta-human chorionic gonadotropin (HCG) was normal. Staging workup included computed tomography chest and ultrasound abdomen (USG) that were normal. The child was treated with standard infantile bleomycin, etoposide, cisplatin-based chemotherapy regimen and showed excellent clinical, radiological, and biochemical recovery.
|Figure 2: (1) Microphotograph shows neoplastic arranged in reticular, microcystic, and papillary pattern against a myxoid background. The cells display moderate nuclear atypia. (H&E stain, ×200) (2) Tumor cells express CK (DAB stain, ×200) (3) Tumor cells are positive for SALL4 (DAB stain, ×100) (4) Tumor cells express Glypican3 (DAB stain × 100)|
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In this study, we present a review of the clinical approach and various differentials of orbital tumors in young children.
| Discussion|| |
Orbital tumors are rare in children accounting for 3.5–4% of childhood tumors. Presenting symptoms may be non-specific and include proptosis, diplopia, or vision complaints. Differentials include a broad list of benign and malignant disorders depending on the location and structure of origin, progression of symptoms, and age of the child. Ascertaining whether the tumor is intraocular or extraocular may help further in deciding diagnostic work-up. In infancy, common benign lesions include vascular malformations and developmental cysts, whereas the most common malignant intraocular tumor is retinoblastoma and the common extraocular intraorbital tumors include metastatic neuroblastoma, rhabdomyosarcoma (RMS), chloroma, and Langerhans cell histiocytosis (LCH). In older children, primitive neuro-ectodermal tumors and lymphoma are the other differentials. However, in the present case, the histology was GCT, which is very rare in this location. Malignant GCT accounts for about 3% of all malignancies in children. The most common sites for extragonadal GCT in young children include sacrococcyx and retroperitoneum, whereas head and neck comprise only 5% of all cases. Reported sites include jaw, cheek, upper lip, the floor of the mouth, and nasopharynx.,,, The most common histological subtype of extragonadal GCT is teratoma, whereas YST as observed in our case is extremely rare. In a large reported series of 15 children with orbital YST, only three were infants. Considering the rarity of orbital tumors in infancy, a high index of suspicion for underlying malignancy is a must to prevent delay in diagnosis as delay may potentially lead to permanent loss of vision.
Orbital USG is a useful initial diagnostic modality as it helps to ascertain the origin, extent, and nature of the lesion, whereas MRI orbit is the modality of choice as it gives better characterization and provides information about the involvement of the optic nerve and intracranial extent. Imaging features suggestive of benign disorders include cystic appearance, internal fat attenuation, and internal calcification (dermoid cyst), and feeder vessels with good contrast enhancement (hemangioma). Orbital involvement in malignant conditions is seen in 5% of RMS, 10% of hematolymphoid malignancies, and 23% of LCH. In orbital RMS, the mass is well-defined, heterogeneous with variable contrast enhancement, involves the extraocular muscles, and is usually associated with erosion of the adjacent bone. Chloroma should be suspected in acute onset bilateral proptosis and generally, these lesions do not cause bone destruction. In such cases, signs of systemic involvement such as hepatosplenomegaly and lymphadenopathy should be looked for and a peripheral blood film and bone marrow examination take precedence over biopsy for diagnosis. Advanced retinoblastoma appears as an intraocular mass with intralesional calcification. Metastasis from neuroblastoma should be considered in a young child presenting with acute-onset proptosis and the USG abdomen may reveal the primary tumor. Lytic lesions in bone radiographs should arouse suspicion of LCH. Thus clinical and radiological features may help plan subsequent work-up. After imaging, careful planning of biopsy and IHC are needed to confirm the underlying pathology. In GCT, elevated AFP/BHCG beta Human Chorionic Gonadotropin levels and serial follow-up are useful for diagnosis, monitoring response, and post-treatment surveillance. In general, orbital YST has a better prognosis than gonadal GCT due to early identification and better response to treatment.
Recent advances in cancer genomics reveal that YSTs show distinct overexpression of genes involved in the WNT/β-catenin and TGF-β/BMP pathways. Analyses of profiled genetic and epigenetic features reveal interesting results. YSTs exhibit overexpression of endodermal genes, such as GATA6 and FOXA2, the binding sites of which were hypomethylated. Furthermore, the DNA methylation patterns in infant YSTs are different from those in older children. These studies are clinically important as they provide critical insights into the molecular mechanisms associated with the YST resistance to chemotherapy.
| Conclusion|| |
Though rare, orbital masses in young children may harbor underlying malignant disorders. Multidisciplinary discussion among pediatric-oncologist, radiologists, pathologists, and ophthalmologists is critical for timely intervention and optimum outcome. Any delay may adversely impact the outcome of vision and survival.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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Department of Pediatric Hematology and Oncology, Rajiv Gandhi Cancer Institute and Research Centre, Sector 5, Rohini, Delhi - 110085
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2]