Saudi Journal of Ophthalmology (2010) 24, 23–26
King Saud University
Saudi Journal of Ophthalmology www.ksu.edu.sa www.sciencedirect.com
CASE REPORT
Malignant fibrous histiocytoma in a patient with history of treated retinoblastoma Hind M. Alkatan, MD a b
a,*
, Azzah Maktabi, MD
b
Department of Pathology and Laboratory Medicine, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia Department of Ophthalmology, Prince Salman Hospital, Riyadh, Saudi Arabia
Received 16 March 2009; accepted 23 June 2009 Available online 4 January 2010
KEYWORDS Retinoblastoma; Orbit; Second tumors
Abstract Retinoblastoma is one of the most important childhood tumors with genetic implications and necessity for family counseling and long term follow up. We are presenting a 22 year-old Saudi male with history of bilateral retinoblastoma, who was initially treated by enucleation of his left eye. The histopathology showed a moderately differentiated tumor with vitreous seeding and he received chemotherapy in addition to radiotherapy to his right eye. He presented 20 years later with a right orbital tumor, frozen globe and proptosis. The excisional biopsy of his orbital mass revealed a spindle cell sarcoma with features of malignant fibrous histiocytoma. His clinical and radiological findings are presented together with the histopathologic features of his orbital tumor and brief review of secondary tumors in retinoblastoma patients. ª 2009 King Saud University. All rights reserved.
1. Introduction Retinoblastoma is one of the most common childhood malignancies. It is responsible for approximately 1% of all deaths from cancer in the paediatric age group (Apple and Rabb, 1998). Greater number of survivors of this tumor is recently * Corresponding author. Address: Pathology and Laboratory Medicine Department, King Khaled Eye Specialist Hospital, P.O. Box 7191, Riyadh 11462, Saudi Arabia. Tel./fax: +966 1 482 1234x3131/3212. E-mail address:
[email protected] (H.M. Alkatan). 1319-4534 ª 2009 King Saud University. All rights reserved. Peerreview under responsibility of King Saud University. doi:10.1016/j.sjopt.2009.12.004
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noted due to the improved cure rates, thus there is an expected increasing incidence of the retinoblastoma-inducing gene throughout the general population (Apple and Rabb, 1998). The incidence of other primary malignancies in hereditary retinoblastoma survivors is estimated to be between 4% and 25% at 10–30 years, respectively (Rozans, 2005). With the advancing methods in the treatment of retinoblastoma by chemotherapy, the risk for secondary neoplasm is expected to be decreased in such patients, compared with cases treated by primary enucleation and radiation (Rozans, 2005). We have encountered a case of malignant orbital tumor in one of our patients with bilateral retinoblastoma and history of radiotherapy. 2. Case report A 22-year-old Saudi male presented initially during his infancy with bilateral retinoblastoma for which enucleation of his left
24 eye was performed. The histopathologic examination of the enucleated globe revealed a multifocal moderately differentiated retinoblastoma with significant vitreous seeding, but no optic nerve invasion or extrascleral extension. His bone marrow biopsy and CSF cytology were negative at that time. His follow up post chemotherapy and external beam radiotherapy to the right eye revealed slightly regressed tumor in that eye and enucleation was advised. The patient was then lost to follow up for 20 years. He presented again with right side proptosis. The right globe showed congested and chemotic conjunctiva with corneal scarring and no further details of the posterior cavity. The Magnetic Resonance Imaging (MRI) revealed large heterogenous soft tissue mass in the right orbital cavity extending to the orbital apex. Another tumor mass with calcification was observed within the globe (Fig. 1). The orbital biopsy showed diffuse abnormal proliferation of variable cells with high degree of pleomorphism, large nuclei and prominent nucleoli. Some of the proliferating cells are spindle in shape with storiform pattern (Fig. 2). Other cells are large, vacuolated with slightly foamy cytoplasm (Fig. 3). These anaplastic cells have a sworling arrangement in a fine collagen matrix and they infiltrate the adipose tissue and the skeletal muscle fibers present with frequent abnormal mitotic figures. The tumor cells were vimentin positive (Fig. 4) and show focal positivity with CD68. The epithelial markers were negative supporting the
H.M. Alkatan, A. Maktabi
Figure 3 Another tumor area with large vacuolated cells (Hematoxylin and Eosin · 400).
Figure 4
Figure 1 Magnetic Resonance Imaging showing right orbital tumor and the residual right intraocular mass.
Positive tumor cells with Vimentin Stain (·400).
diagnosis of a sarcoma. Other negative stains include: S100, HMB-45, Desmin, Myogenin, Muscle Specific Actin, and CD34. The final diagnosis was: malignant fibrous histiocytoma (MFH) of the right orbit. 3. Discussion
Figure 2 Histopathologic appearance of the tumor cells with storiform pattern (Hematoxylin and Eosin · 25).
Fibrous histiocytomas are mesenchymal tumors that involve soft tissues being the most common adult mesenchymal tumor of the orbit (Rootman, 2003). It was first described in 1960 and the orbit was then identified as site of predilection by Zimmerman in 1967. The neoplasm is characterized by infiltrative features, tendency for local recurrence, rare metastasis and a biological behavior which parallels the histopathologic features. The benign type is the most common. The intermediate type has increased cellularity and few mitotic figures. The least frequent is the malignant type which can arise ‘‘de novo’’ or following orbital radiotherapy. Rootman (2003) encountered three cases of orbital malignant fibrous histiocytoma (MFH) in his series and one of these developed in the orbit of a child with history of retinoblastoma. Shields et al. (2001) reviewed major reports of second cancer after radiation for retinoblastoma and found three fibrous histiocytomas among 112 secondary tumors
Malignant fibrous histiocytoma in a patient with history of treated retinoblastoma therefore contributing to an incidence of 2.6%. They also reported a case of (MFH) with confirmation of the diagnosis by histopathology, immunohistochemical and ultrastructural findings. Other reported secondary tumors (Font and Hidayat, 1982; Dally, 1999; Font et al., 1983; Abramson et al., 1984; Roarty et al., 1988; Sagerman et al., 1969; Abramson and Frank, 1998; Schlienger et al., 1985; Charis et al., 1993; Fontanesi et al., 1995; Traboulsi et al., 1988) include osteogenic sarcoma as the most common secondary tumor with 500 times higher prevalence in such patients than in general population. Less frequent tumors are fibrosarcoma, leiomyosarcoma, rhabdomyosarcoma, and cutaneous tumors including malignant melanoma, squamous cell carcinoma, sebaceous carcinoma and basal cell carcinoma. Radiologically it is difficult to distinguish (MFH) from other orbital masses. In these cases, the enhancement pattern on Computed Tomography (CT) or MRI may be inhomogeneous with avascular or necrotic non-enhancing regions (Dally, 1999). The pathogenesis of secondary tumors in survivors of retinoblastoma has been extensively studied and the classical concept of ‘‘radiocancer’’ is generally admitted with variable latent period for the appearance of the common secondary tumors ranging between 14.3 and 11 years for osteogenic sarcoma, and between 16 and 12 years for other soft tissue sarcoma as studied by Font et al. (1983). Abramson also concluded a 10.4 years mean latent period of second tumors in retinoblastoma survivors which favors radiation inducement as an etiology in the pathogenesis of such tumors (Abramson et al., 1984). The other factor which supports this relation is the 30 years cumulative incidence of second neoplasm in bilateral retinoblastoma reported by Roarty et al. (1988) to be 35.1% in patients who received radiation, compared to 5.8% in patients who did not receive radiation. Second tumors rate was also found to be 29.3% within the field of radiation and only 8.1% outside the field. In regard to the dose of radiation, Sagerman et al. (1969) demonstrated a dose–response curve for incidence of second tumors in relation to the radiation dose. On the other hand Abramson et al. (1984) failed to demonstrate a relationship between the incidence and the dose of therapeutic radiation. Then Zimmerman (Roarty et al., 1988) commented that the higher risk in these survivors can be attributed to the old methods and the excessive doses of radiation used for treatment at that time. Abramson further considered the age at the time of radiation as an important factor and concluded that irradiation before the age of 12 months is a risk factor (Abramson and Frank, 1998). However, the fact that some of these tumors develop in a different location from the irradiated area definitely raises the possibility of other predisposing factors, most importantly the genetic factor (Schlienger et al., 1985). The prognosis in general shows a cumulative probability of death from second neoplasm of 26% at 40 years after bilateral retinoblastoma (Charis et al., 1993). Unfortunately MFH are generally high grade sarcomas with tendency for local recurrence and possible distant metastasis (Dally, 1999). This was evident in our patient where his systemic work-up and bone scan revealed a metastatic lesion in the neck of the left femur. The histopathology of the biopsy revealed an undifferentiated sarcoma considered to be metastatic from his orbital lesion rather than being an osteogenic sarcoma (Fig. 5). He
25
Figure 5 The histopathologic appearance of the metastatic lesion of the femoral neck (Hematoxylin and Eosin · 400).
received radiotherapy with poor response and the disease progressed with metastatic lesions in submandibular, pre and post auricular lymph nodes. In conclusion, carriers of the retinoblastoma gene have an increased incidence for secondary tumors, which is augmented by radiation therapy. Ophthalmologists should always keep this in mind to be able to provide these patients with proper counseling, plan for close long term follow up and update their knowledge in the field of retinoblastoma management. References Abramson, D.H., Frank, C.M., 1998. Second nonocular tumors in survivors of bilateral retinoblastoma. Ophthalmology 105, 573– 579. Abramson, D.H., Ellsworth, R.M., Kitchin, F.D., Tung, G., 1984. Second nonocular tumors in retinoblastoma survivors. Ophthalmology 91, 1351–1355. Apple, D.J., Rabb, M.F., 1998. Retinoblastoma, leukokoria, and phakomatoses. In: Ocular Pathology, fifth ed. Mosby, St. Louis, USA. Charis, E., Frederick, P.L., Abramson, D.H., Ellsworth, R.M., Wong, L., et al., 1993. Mortality from second tumors among long-term survivors of retinoblastoma. J. Natl. Cancer Inst. 85 (14), 1121– 1128. Dally, R.W., 1999. Fibrous histiocytoma and fibrous tissue tumors of the orbit. Radiol. Clin. North Am. 37 (1), 185–194. Font, R.L., Hidayat, A.A., 1982. Fibrous histiocytoma of the orbit. A clinicopathologic study of 150 cases. Hum. Pathol. 13, 199–209. Font, R.L., Jurco, S., Brechner, R.J., 1983. Post radiation leiomyosarcoma of the orbit complicating bilateral retinoblastoma. Arch. Ophthalmol. 101, 1557–1561. Fontanesi, J., Parham, D.M., Pratt, C., Meyer, D., 1995. Second malignant neoplasms in children with retinoblastoma. The St Jude children’s research hospital experience. Ophthal. Genet. 16 (3), 105–108. Roarty, J.D., Mclean, I.W., Zimmerman, L.E., 1988. Incidence of second neoplasms in patients with bilateral retinoblastoma. Ophthalmology 95, 1583–1587. Rootman, J., 2003. Neoplasia. In: Diseases of the Orbit – A Multidisciplinary Approach, second ed. Lippincott Williams and Wilkins, Philadelphia. Rozans, M.K., 2005. Chemotherapy for childhood tumors. In: Karcioglu, Z.A. (Ed.), Orbital Tumors, Diagnosis and Treatment. Springer, NY, USA.
26 Sagerman, R.H., Cassady, J.R., Tretter, P., Elsworth, R.M., 1969. Radiation induced neoplasia following external beam therapy for children with retinoblastoma. Am. J. Roentgenol. Radium. Schlienger, P., Calle, R., Haye, C., Vilcoq, J.R., 1985. Bone sarcoma and malignant tumors of the retina. B Cancer 72 (1), 16–24. Shields, J.A., Husson, M., Shields, C.L., Krema, H., Eagle, R.C., Singh, A.D., 2001. Orbital malignant fibrous histiocytoma follow-
H.M. Alkatan, A. Maktabi ing irradiation for retinoblastoma. Ophth. Plast. Reconstr. Surg. 17 (1), 58–61. Traboulsi, E.L., Zimmerman, L.E., Manz, H.J., 1988. Cutaneous malignant melanoma in survivors of heritable retinoblastoma. Arch. Ophthalmol. 106 (8), 1059–1061.
