|Ahead of print
Primary yolk sac tumor of orbit: Report of a rare case
Sandhya V Poflee1, Prajkta S Pawar1, Nilesh S Gaddewar2, Waman K Raut1
1 Department of Pathology, Government Medical College, Nagpur, Maharashtra, India
2 Department of Opthalmology, Government Medical College, Nagpur, Maharashtra, India
|Date of Submission||05-Sep-2018|
|Date of Decision||22-Nov-2018|
|Date of Acceptance||27-Dec-2018|
|Date of Web Publication||22-Jun-2020|
Prajkta S Pawar,
Department of Pathology, Government Medical College, Nagpur, Maharashtra
Source of Support: None, Conflict of Interest: None
Extragonadal germ cell tumors (GCTs) of head and neck region account for 5% of all benign and malignant GCTs. Orbit is an uncommon site for occurrence of extragonadal GCTs. Pure yolk sac tumor (YST) of orbit is a rare neoplasm and only a few cases are reported in the literature. An 18-month-old boy presented with right eye proptosis of 2 months duration. Because of rapid clinical course and magnetic resonance imaging (MRI) findings, neoplastic lesion was suspected. Histopathological examination of the biopsy revealed neoplasm with possibility of GCT. Raised serum alpha-feto-protein levels suggested YST component. Positivity for immunohistochemical markers Glypican-3 and SALL4 confirmed pure YST nature of the tumor. The child received six cycles of cisplatin-based chemotherapy with significant reduction in size of the tumor, followed by exenteration of the orbit. This case is reported for its rarity as well as for highlighting diagnostic characteristics and management of orbital YST.
Keywords: Childhood orbital tumor, immunohistochemistry, yolk sac tumor
| » Introduction|| |
Extragonadal germ cell tumors (EGGCTs) of head and neck region comprise about 5% of all benign and malignant germ cell tumors (GCTs). Among extragonadal sites, orbital GCTs are rare, and most of them are teratomas. Pure yolk sac tumor (YST) of orbit is uncommon, and only a few cases are on record.,
| » Case Report|| |
An 18-month-old boy presented to ophthalmic outpatient department with redness of eye and rapidly increasing right orbital swelling of 2 months duration [Figure 1]a. There was significant protrusion of the right eyeball since 15 days. No other complaints were mentioned by his parents. Developmental milestones of the child were normal and no abnormal findings were noted on general examination.
|Figure 1: [a] Patient photograph at presentation. [b] Magnetic resonance imaging of head showing right orbital mass. [c] Microphotograph showing tumor cells in reticular pattern with formation of duct-like structures and microcysts (H and E 40×). [d] Pools of basophilic myxoid material and sparse spindle cells (H and E 40×)|
Click here to view
On ocular examination, proptosis and lagophthalmos were present in the right eye. There was lid edema and a hard mass was palpated in superior part of orbit. Conjunctival congestion was present and cornea showed changes of exposure keratopathy. Vision of right eye was totally lost while left eye was normal.
Magnetic resonance imaging (MRI) of head and neck region revealed a well-defined, fusiform heterogeneous signal intensity lesion of size 2.7 × 3.8 × 2.8 cm, predominantly involving extraconal component of right orbit with a small intraconal component. Right lacrimal gland was visualized separately from the lesion. The lesion was isointense to muscle on T1 weighted images and isointense-hyperintense to muscle on T2 weighted images [Figure 1]b. Imaging diagnosis was hemangioma or rhabdomyosarcoma.
Biopsy of tumor and periorbital tissue was performed. Sections showed uninvolved adipose tissue and a tumor mass comprising pools of basophilic myxoid material with sparse spindle cells and prominent blood vessels [Figure 1]d. There was formation of duct-like structures, acini, and microcysts that were lined by cuboidal cells with vacuolated cytoplasm [Figure 1]c. Schiller-Duval bodies and extracytoplasmic and intracytoplasmic hyaline globules were not identified. Histological diagnosis of neoplasm with possibility of GCT was suggested and immunohistochemistry was advised.
Raised serum alpha-feto-protein (AFP) levels of more than 1,210 ng/mL suggested yolk sac component. Initial immunohistochemical (IHC) workup showed that tumor cells were positive for pancytokeratin (PANCK) but negative for epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA), calponin, smooth muscle actin, and CK14 which ruled out the possibility of epithelial and myoepithelial neoplasms of lacrimal gland. Negativity for desmin and myogenin ruled out the possibility of rhabdomyosarcoma and negativity for HMB45 and S100 ruled out the possibility of melanoma. Specific IHC markers were applied for confirmation of GCT. Negativity of tumor cells for OCT3, OCT4, and CD117 ruled out the possibility of embryonal carcinoma or seminoma of a mixed GCT. The tumor showed immunopositivity for AFP, glypican-3, SALL4, PANCK and CK 19 which confirmed the diagnosis of pure YST [Figure 2]a, [Figure 2]b, [Figure 2]c, [Figure 2]d.
|Figure 2: Immunohistochemistry images. [a] Tumor cells showing cytoplasmic positivity for glypican-3, [b] nuclear positivity for SALL4, [c] Negativity for OCT3/4, and [d] negativity for CD117. [e] Photograph of patient after six cycles of chemotherapy|
Click here to view
Detailed clinical examination of the patient did not show any other mass lesion. On genital examination, bilateral scrotal testes were present. On chest X-ray and abdominopelvic ultrasonography, there was no evidence of mass lesion which confirmed primary nature of the orbital tumor.
The patient received six cycles of cisplastin-based chemotherapy, with significant reduction in tumor size [Figure 2]e. Exenteration of right orbit was performed after completion of chemotherapy. Histopathology of exenteration specimen did not reveal any residual tumor. Post-surgery patient is under monthly clinicoradiological follow-up since 1 year with no recurrence of tumour.
| » Discussion|| |
Developmental cysts and benign tumors form most of pediatric orbital mass lesions. The most common childhood orbital malignancy is rhabdomyosarcoma, while the most common intraocular malignant neoplasm is retinoblastoma. Pure YST in the orbit is rare.,
YST arises commonly within the gonads. YST also occurs at various extragonadal sites such as sacrococcyx, retroperitoneum, mediastinum, brain, and head and neck area. Tumors in these sites are believed to originate from germ cells that have been misplaced or arrested in their embryonic migration.
YSTs usually occur in infants and young children. Female preponderance is seen in reported cases of orbital YST. Male sex of the child in our case adds to its rarity. Common clinical presentation of orbital YST is unilateral and is rapidly progressive and with massive proptosis. The tumor frequently invades the periorbital and intracranial spaces giving rise to extraocular manifestation., On MRI, tumor appears as a mass lesion of relatively heterogeneous signal intensity.
On gross examination, YSTs appear as gray to yellow, solid-cystic in consistency with areas of hemorrhage and necrosis on cut surface. Microscopically, YSTs show intermingling of epithelial and mesenchymal element in an organoid fashion. Microcystic, glandular-alveolar, and papillary formations lined by flattened or cuboidal cells are seen. The stroma may be myxoid, containing spindle/stellate cells. Perivascular Schiller-Duval bodies and hyaline intracytoplasmic and extracytoplasmic round inclusions are consistently seen in YSTs.
In all, 98% patients of YST show elevated serum AFP levels. Raised levels are useful for diagnosis, in monitoring response to therapy, and prognosis of YST. Glypican-3 is a sensitive IHC marker and is positive in almost all cases. SALL4 and PANCK are uniformly immunoreactive. Negativity of YST for OCT3/4, CD30, and CD117 is helpful for differentiating it from embryonal carcinoma and seminoma. Our case was positive for AFP, Glypican-3, SALL4, and PANCK, and negative for OCT3/4 and CD117 which ruled out the possibility of mixed GCT and confirmed the pure nature of YST.
YST is treated with multimodality therapy consisting of cisplatin-based combination chemotherapy with surgery and/or radiotherapy. Surgical excision with chemotherapy is the ideal regimen for improving outcome as radiotherapy has adverse effects on the growing child, while surgery eradicates the genetically altered tissue at the tumor bed. Orbital YST has better prognosis than visceral EGGCT due to early recognition and prompt treatment. YST, limited to orbit, managed by extensive surgery and chemotherapy seemed to have better long-term disease-free survival.
Differential diagnosis of rapidly growing orbital masses in infants and young children should include YST even at unusual extragonadal location like orbit. Confirmation of diagnosis is possible with histopathological examination of the tumor tissue, serum AFP level estimation, and application of specific and sensitive panel of IHC markers. Definitive diagnosis has important role in management, planning, and prediction of prognosis in orbital YST.
We are thankful to department of radiotherapy, Government Medical College and Hospital, Nagpur for giving therapy details. We are thankful to Dr. Sanjay Navani for immunohistochemistry results.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient' parents have given their consent for the images and other clinical information to be reported in the journal. The patient's parents understand that the names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| » References|| |
Kusuma Kumari P, Geetha N, Chellam VG, Nair MK. Endodermal sinus tumors in the head and neck region. Med Pediatr Oncol 1997;29:303-7.
Kamal S, Kaliki S, Sreedhar A, Mishra D. Primary orbital yolk sac tumor: Report of a case and review of literature. Int Ophthalmol 2016;36:435-44.
Ahmad Z, Khurshid A, Qureshi A. Primary orbital yolk sac tumour in a 14-year-old girl. BMJ Case Rep. 2009;2009:bcr04.2009.1821. doi: 10.1136/bcr. 04.2009.1821.
Kiratli H, Erkan Balci K, Guler G. Primary orbital endodermal sinus tumor (yolk sac tumor). J AAPOS 2008;12:623-5.
Castillo BV Jr, Kaufman L. Pediatric tumors of the eye and orbit. Pediatr Clin North Am 2003;50:149-72.
Clement PB, Young RH. Pathology of extragonadal yolk sac tumors. In: Nogales FF, editor. The Human Yolk Sac and Yolk Sac Tumors. Berlin, Heidelberg: Springer; 1993. p. 285-308.
Devaraja K, Sikka K, Singh PK. Peculiarities of yolk sac tumor in head and neck: A case report and literature review. Indian J Med Paediatr Oncol 2018;39:260-2. [Full text]
Rosai J. Rosai and Ackerman's Surgical Pathology. 9th
ed, vol 1. St. Louis: Mosby, Elsevier Inc; 2009. p. 1430-36.
Moch H, Humphrey PA, Ulbright TM, Reuter VE, editors. WHO Classification of Tumours of the Urinary System and Male Genital Organs. 4th
ed. Lyon: International agency for research on cancer; 2016. p. 185-226.
[Figure 1], [Figure 2]