Malignant rhabdoid tumor is a rare childhood tumor that was first described as an aggressive variant of Wilm's tumor1,2 because it commonly arises in the kidneys. It is now known that it may also affect other tissues.
Several cases of malignant extrarenal rhabdoid tumor involving the orbit have been described as both primary forms or metastases.3–11 Further reports include one described as an intraocular metastasis12 and one as an intraocular primary tumor without systemic involvement.1
The radiological features and imaging of malignant rhabdoid tumor are unspecific but serve to assess the extent of the tumor. Histological and immunohistochemical findings are key to diagnosis. At the molecular level, malignant extrarenal rhabdoid tumor is defined in terms of mutations or modifications in the tumor-suppressor gene SMARCB1/INI1 on chromosome 22q11.2, which leads to a lack of INI1 gene expression.13
Intraocular primary malignant extrarenal rhabdoid tumor is rare. As far as the authors are aware, there is only the single case mentioned above reported in the medical literature.1
A 13-year-old boy was referred by an outside ophthalmologist to the authors' clinic because of a visible whitish intraocular mass, red eye, and complaints of gradual vision loss in the left eye during the past 8 months. The patient had a history of headaches and no other medical history of interest.
Visual acuity without correction was 20/20 in the right eye and light perception in the left eye. Intraocular pressure was 17 mm Hg in the right eye and 50 mm Hg in the left eye. On slit-lamp examination, a normal right eye and a red left eye with a shallow anterior chamber, a whitish mass protruding through the pupil, posterior synechia, and atrophy of the inferior temporal iris were observed. Episcleral blood vessels were engorged and there was neovascularization of the iris (Figure 1).
Slit-lamp photograph of the left eye showing a red eye with a shallow anterior chamber, a white-yellow mass protruding through the pupil, posterior synechia, and inferior temporal iris atrophy. Also appreciable were engorged episcleral vessels and iris neovascularization.
Ocular ultrasonography and ultrasonographic biomicroscopy revealed a temporal bi-lobulated chorioretinal hyperechoic mass measuring 10 mm at the base and 7 mm in height with internal vascularization and internal hypoechoic zones. There was invasion of the ciliary body and anterior chamber (Figure 2). On orbital computed tomography, an intraocular tissue mass measuring 11 × 9 mm was seen on the left side of the left eye, which was vascularized and contacted the lens without extraocular involvement.
(A) Ocular ultrasonography. (B) Ultrasonographic biomicroscopy revealed a temporal bi-lobulated chorioretinal mass, measuring 7 mm at the base and 5 mm in height, with internal vascularization. There was invasion of the ciliary body and anterior chamber.
On suspicion of a malignant intraocular tumor with a poor visual prognosis, the globe was urgently enucleated and a 22-mm, porous, polyethylene, spherical orbital implant was inserted. On gross examination, the tumor appeared as a whitish intraocular nodule with a maximum size of 10 mm.
Microscopy examination showed the proliferation of large cells with an eosinophilic cytoplasm, atypical eccentric nucleus, and prominent nucleoli. Twelve mitoses per 10 high-power fields (×400) were counted, along with necrotic foci and invasion of the posterior iris and ciliary body without extrascleral involvement or tumor spread to the optic nerve. Immunohistochemical studies revealed loss of the INI1 gene and focal positivity for the epithelial membrane antigen, neurofilaments, and CD99. A few cells were positive for neuron-specific enolase and protein S100 and melan-A were negative (Figure 3). According to these observations, a diagnosis of intraocular malignant rhabdoid tumor without extraocular involvement was made.
(A) Microscopy observation of proliferating large cells with an eosinophilic cytoplasm, a typical eccentric nucleus and prominent nucleoli (arrows). (B) Immunohistochemical staining. INI1 staining showing (a) positive staining in endothelial cells and (b) loss of immunoreactivity in rhabdoid tumor cells.
A hematological examination and thorough systemic work-up ruled out another primary tumor or metastasis. The patient remains under strict follow-up.
Malignant rhabdoid tumor is a highly aggressive, rare cancer that most commonly affects the kidney. Mortality is 80%. It occurs more frequently in male infants. The tumor can metastasize to the brain or invade the central nervous system or other soft tissues.14
Primary intraocular malignant rhabdoid tumor is classified within the malignant extrarenal rhabdoid tumors. The case described in the medical literature of a primary intraocular malignant extrarenal rhabdoid tumor1 was also that of a male patient, although much younger than ours and with extrascleral involvement. To date, this is the first report of an exclusively intraocular primary malignant rhabdoid tumor. Malignant extrarenal rhabdoid tumor is resistant to multimodal therapy with chemotherapy and adjuvant radiotherapy, and thus shows a low disease-free survival rate and grim prognosis.4,9,10 Treatment of the current patient consisted only of enucleation because no evidence was detected of a primary tumor at the systemic level.
The differential diagnosis of malignant extrarenal rhabdoid tumor includes tumors such as rhabdomyosarcoma, neuroblastoma, lymphoma, Ewing sarcoma, neuroectodermal tumor, and malignant melanoma. Immunohistochemical studies are mandatory to establish the correct diagnosis. Malignant rhabdoid tumor shows a characteristic pattern of immunoreactivity for vimentin, cytokeratin, and epithelial membrane antigen, whereas it is negative for muscle markers (desmin and myoD1), histiocytic markers, or melanocytic markers (HMB45 and S100 protein), thus excluding myogenic, histiocytic neoplasms, or malignant melanoma.15 In addition, some cases show focal positivity for neurofilaments, neuron-specific enolase, and CD99, as occur in this case.
The loss or mutation of the INI1 (SMARCB1) tumor-suppressing gene is a known oncogenic factor associated with malignant rhabdoid tumor.13 This fact can be demonstrated by the loss of INI1 immunohistochemical expression in the tumoral cells, and is an essential marker to confirm the diagnosis (Figure 3B).
Although no evidence of a primary tumor was detected in the systemic assessment, our patient is under strict follow-up. This is because of the aggressive nature of malignant rhabdoid tumor and the possibility that a primary non-intraocular tumor might be detected at some point.
The tumor was diagnosed and treated early, and the patient is currently well. However, the management of primary intraocular malignant rhabdoid tumor is a challenge owing to a lack of reports of treatment of intraocular malignant extrarenal rhabdoid tumor without extraocular involvement, the variable presentation of malignant extrarenal rhabdoid tumor, both clinically and histopathologically, and the prognosis, which seems to vary according to age.
Primary intraocular malignant extrarenal rhabdoid tumor is extremely rare. Its diagnosis is essentially based on histopathological and immunohistochemical findings. It is important to rule out primary renal malignant rhabdoid tumor and metastasis. Because of its rarity, there are scarce data available, so it is also important that all cases are reported.
- Shah SJ, Ali MJ, Mulay K, Honavar SG, Reddy VA. Primary intraocular malignant extrarenal rhabdoid tumor: a clinicopathological correlation. J Pediatr Ophthalmol Strabismus. 2013;50:e18–e20.
- Beckwith JB, Palmer NF. Histopathology and prognosis of Wilm's tumor: results from the first national Wilm's tumor study. Cancer. 1978;41:1937–1948. doi:10.1002/1097-0142(197805)41:5<1937::AID-CNCR2820410538>3.0.CO;2-U [CrossRef]
- Rootman J, Damji KF, Dimmick JE. Malignant rhabdoid tumors of the orbit. Ophthalmology. 1989;96:1650–1654. doi:10.1016/S0161-6420(89)32666-2 [CrossRef]
- Gündüz K, Shields JA, Eagle RC, Shields CL, De Potter P, Klombers L. Malignant rhabdoid tumor of the orbit. Arch Ophthalmol. 1998;116:243–246. doi:10.1001/archopht.116.2.243 [CrossRef]
- Walford N, Defferai R, Slater RM, et al. Intraorbital rhabdoid tumor following bilateral retinoblastoma. Histopathology. 1992;20:170–173. doi:10.1111/j.1365-2559.1992.tb00948.x [CrossRef]
- Watanabe H, Watanabe T, Kaneko M, et al. Treatment of unresectable malignant rhabdoid tumor orbit with tandem high-dose chemotherapy and gamma-knife radiosurgery. Pediatr Blood Cancer. 2006;47:846–850. doi:10.1002/pbc.20699 [CrossRef]
- Seeringer A, Reinhard H, Hasselblatt M, et al. Synchronous congenital malignant rhabdoid tumor of the orbit and atypical teratoid/rhabdoid tumor-feasibility and efficacy of multimodal therapy in a long-term survivor. Cancer Genet. 2014;207:429–433. doi:10.1016/j.cancergen.2014.06.028 [CrossRef]
- Jakobiec FA, Callahan AB, Stagner AM, et al. Malignant rhabdoid transformation of a longstanding, aggressive, and recurrent orbital angiomyxoma. Surv Ophthalmol. 2015;60:166–176. doi:10.1016/j.survophthal.2014.12.002 [CrossRef]
- Gottlieb C, Nijhawan N, Chorneyko K, O'Grady KF, Harvey JT. Congenital orbital and disseminated extrarenal malignant rhabdoid tumor. Ophthal Plast Reconstr Surg. 2005;21:76–79. doi:10.1097/01.IOP.0000150353.90937.B4 [CrossRef]
- Kook KH, Park MS, Yim H, Lee SY, Jang JW, Grossniklaus HE. A case of congenital orbital malignant rhabdoid tumor: systemic metastasis following exenteration. Ophthalmologica. 2009;223:274–278. doi:10.1159/000213643 [CrossRef]
- Karaman S, Celkan T, Dervsoglu S, et al. Malignant rhabdoid tumor of the orbit [article in Turkish]. Turk Patoloji Derg. 2013;29:69–72.
- Akhtar M, Ali MA, Sackey K, Bakry M, Johnson T. Malignant rhabdoid tumor of the kidney presenting as intraocular metastasis. Pediatr Hematol Oncol. 1991;8:33–43. doi:10.3109/08880019109033425 [CrossRef]
- Versteege I, Sévenet N, Lange J, et al. Truncating mutations of hSNF5/INI1 in aggressive paediatric cancer. Nature. 1998;394:203–206. doi:10.1038/28212 [CrossRef]
- Weeks DA, Beckwith JB, Mierau GW, Luckey DW. Rhabdoid tumor of kidney. A report of 111 cases from the National Wilms' Tumor Study Pathology Center. Am J Surg Pathol. 1989;13:439–458. doi:10.1097/00000478-198906000-00001 [CrossRef]
- Haas JE, Palmer NF, Weinberg AG, Beckwith JB: Ultrastructure of malignant rhabdoid tumor of the kidney: a distinctive renal tumor of children. Hum Pathol. 1981;12:646–657. doi:10.1016/S0046-8177(81)80050-0 [CrossRef]