PEDIATRIC NASOPHARYNGEAL CARCINOMA WITH RETINAL METASTASIS Armando Alegret, MD, Colleen M. Cebulla, MD, PHD, Sander R. Dubovy, MD, Lejla Mutapcic, MD, Ditte J. Hess, CRA, Timothy G. Murray, MD, MBA
Purpose: To report an unusual case of nasopharyngeal carcinoma (NPC) metastatic to the lungs and retina. To our knowledge, this is the first report of retinal metastasis from NPC. Design: Observational case report. Methods: We studied the case of a 15-year-old boy who had been recently diagnosed with metastatic NPC and was referred for evaluation of a suspicious retinal lesion in the right eye. Results: Clinical examination and fundus photography showed an amelanotic, 1-diskarea infiltration in the retina along the inferotemporal arcade that was suggestive of metastatic disease. The lesion was small and irregularly shaped by echographic examination, and a nodular area of retinal thickening was seen by optical coherence tomography. Pathologic analysis of lung biopsy and nasopharynx biopsy specimens revealed undifferentiated NPC. Conclusions: Retinal metastases need to be considered in the differential diagnosis of patients presenting with NPC and vision changes. RETINAL CASES & BRIEF REPORTS 3:8 –11, 2009
From Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami, Miller School of Medicine, and the Florida Lions Ocular Pathology Laboratory, Miami, Florida.
an incidence of 0.5 to 2 cases per 100,000 population. It has a bimodal age distribution, with a small peak observed in late childhood and a second peak occurring in people 50 to 60 years of age as reported by Vokes et al.3 In contrast to other epidermoid carcinomas of the head and neck, the undifferentiated type of NPC (World Health Organization type III) has a clear association with Epstein-Barr virus serology and no direct correlation with alcohol or tobacco.3,4 In contrast to other epidermoid cancers of the head and neck, NPC has a greater tendency for early metastatic spread.3–5 Metastases are usually present at the initial presentation and increase in frequency in advanced disease and in recurrent tumors. Altun et al4 reported that lymph node metastases occur in 75% to 90% of patients with NPC; distant metastases typically involve the lungs, skeleton, and liver. Ocular involvement is exceptionally rare, with only a few case reports of choroidal involvement6 – 8 and no reports of retinal involvement to our knowledge. Herein,
A
lthough metastatic carcinoma to the choroid is considered the most common intraocular neoplasm, metastases limited to the retina remain extremely rare occurrences.1 Bloch and Gartner2 described 4 cases of retinal metastasis among 230 patients with autopsy-proven carcinomas originating from various primary sites. To our knowledge, there are only a few reports of nasopharyngeal carcinoma (NPC) metastatic to the choroid and no reports in the literature documenting retinal metastasis. NPC is a squamous cell carcinoma that occurs in the epithelial lining of the nasopharynx. In the United States and Western Europe, NPC is a rare tumor with Reprint requests: Timothy G. Murray, MD, Bascom Palmer Eye Institute, PO Box 016880, Miami, FL 33101; e-mail: [email protected]
8
PEDIATRIC NPC WITH RETINAL METASTASIS
9
Fig. 1. Magnetic resonance imaging (MRI) of nasopharyngeal carcinoma. Axial MRI shows the primary nasopharyngeal carcinoma involving the left nasopharyngeal soft tissue (arrow; A). Chest computed tomography demonstrating metastatic disease in the lung (arrows; B).
we report a rare case of NPC with metastases to the retina and lungs. Case Report A 15-year-old boy was referred to the ocular oncology service for evaluation of a suspicious retinal lesion in the right eye. His medical history was significant for an undifferentiated NPC (World
Fig. 2. Color fundus photography of the right eye shows a retinal infiltrate along the inferior arcade (arrow; A) and a close-up view (arrow; B). Echographic examination demonstrating a small, irregularly shaped lesion at 7:30 posterior to the equator that measured 3.0 ⫻ 3.5 ⫻ 1.1 mm (arrow; C). Optical coherence tomography through the lesion illustrating the retinal infiltrate (arrow; D).
Health Organization type III disease), diagnosed 1 year prior, and metastatic disease to the lungs developing in the following months (Fig. 1). Best-corrected vision was 20/20 in each eye, and intraocular pressure was 17 mmHg in the right eye and 20 mmHg in the left eye. Funduscopic examination of the right eye was remarkable for an amelanotic, 1-disk-area infiltration in the retina along the inferotemporal arcade (Fig. 2, A and B) that was consistent with primary metastatic involvement. Otherwise, the macula, vessels,
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Fig. 3. Histopathologic examination of the nasopharynx biopsy specimen (A and B) discloses nests of pleomorphic basophilic cells (arrow; A: stain, hematoxylin– eosin; original magnification, ⫻100). More magnified views of the area are shown in B (arrow; original magnification, ⫻400). C and D, Histopathologic examination of the lung biopsy specimen. Epstein-Barr virus– encoded RNA immunohistochemical staining discloses positively stained tumor cells (dark blue staining; arrow) within the lung biopsy specimen (C; original magnification, ⫻400). D, Thyroid transcription factor-1 staining is negative within the tumor cells (small arrow) and positive (brown staining) within the normal lung epithelial cells (large arrowhead) (D; original magnification, ⫻200).
and periphery were unremarkable. Initial echographic examination showed a small, irregularly shaped lesion at 7:30 posterior to the equator that measured 3.0 ⫻ 3.5 ⫻ 1.1 mm (Fig. 2C). The lesion was too small to evaluate with A-scanning. No extraocular extension was detected. A nodular area of retinal thickening was seen by optical coherence tomography (Fig. 2D). Fluorescein angiography revealed lesional early hyperfluorescence, late staining, and no leakage. Results of histopathologic analysis of the nasopharynx and lung biopsy specimens were consistent with undifferentiated NPC (Fig. 3). Pleomorphic basophilic cells with hyperchromatic nuclei were detected in nests within the epithelium of the nasopharynx, and there were foci of deep invasion into the subepithelial stroma (Fig. 3, A and B). Similar basophilic cells were detected in the lung biopsy specimen (Fig. 3, C and D). Immunostaining of the lung biopsy specimen was positive for Epstein-Barr virus– encoded RNA, documenting the presence of Epstein-Barr virus antigens. The tumor cells were not reactive for thyroid transcription factor-1, a lung epithelial cell marker; however, the adjacent normal lung tissue was positive (Fig. 3D), thus suggesting evidence against primary lung carcinoma. The patient was treated with external-beam radiation therapy (2,160 cGy) and additional aggressive chemotherapeutic management. Chemotherapy initially consisted of a combination of 5-fluorouracil and cisplatin. This regimen failed, and treatment was then switched to a combination of paclitaxel and carboplatin. The latter
regimen also failed, and treatment with Capecitabine was subsequently started. After chemoradiation therapy, ophthalmoscopic examination, fundus photography, as well as echographic examination of the retinal lesion showed a decrease in both the basal dimension and the apical height. Vision remained 20/20 in both eyes. There were no other retinal or choroidal lesions.
Discussion Intraocular metastases to the retina are extremely rare.1,9 To our knowledge, there are no previous case reports in the literature documenting retinal metastasis from NPC, and there are only three reports of choroidal metastasis.6 – 8 External-beam radiation therapy was well tolerated in the management of this case and was associated with a decrease in the size of the retinal metastasis by ultrasonography. Tissue diagnosis from the retinal lesion would have been ideal; however, in this case, obtaining a tissue biopsy specimen would not have been appropriate given the child’s good vision and the following circumstances: the patient was known to have metastatic disease to other organs (lungs) and a new lesion to the
11
PEDIATRIC NPC WITH RETINAL METASTASIS
retina; the retinal lesion had a shape and density consistent with a mass lesion, ruling out gliosis, cotton-wool spots, or other masquerading lesions; and the retinal lesion was a new finding (not present at prior examinations), ruling out congenital lesions such as astrocytic hamartomas. Radiation therapy is the mainstay of treatment of most primary NPCs, with chemotherapy being used in advanced cases. Because the field of radiation is near the eyes, radiation toxicity may be a cause of decreased vision in these patients, as documented by Parsons et al.10 Retinal– choroidal metastases need to be considered as well in the differential diagnosis of patients presenting with NPC and vision changes. Key words: nasopharyngeal carcinoma, retinal metastasis, squamous cell carcinoma. References 1.
Pelzek CD, Schachat AP. Retinal metastases. In: Ryan SJ, ed. Retina. St. Louis, MO: Mosby; 2001:608–616.
2. 3. 4.
5.
6.
7. 8.
9.
10.
Bloch RS, Gartner S. The incidence of ocular metastatic carcinoma. Arch Ophthalmol 1971;85:673–675. Vokes EE, Liebowitz DN, Weichselbaum RR. Nasopharyngeal carcinoma. Lancet 1997;350:1087–1091. Altun M, Fandi A, Dupuis O, et al. Undifferentiated nasopharyngeal cancer (UCNT): current diagnostic and therapeutic aspects. Int J Radiat Oncol Biol Phys 1995;32:859–877. Hsu MM, Tu SM. Nasopharyngeal carcinoma in Taiwan. Clinical manifestations and results of therapy. Cancer 1983; 52:362–368. Ozyar E, Kiratli H, Akbulut S, et al. Choroid metastasis of undifferentiated nasopharyngeal carcinoma. J Laryngol Otol 1998;112:667–669. Sham JS, Choy D. Choroid metastasis from nasopharyngeal carcinoma. Eur J Surg Oncol 1991;17:384–387. Biswal BM. Restoration of vision following combination chemotherapy of nasopharyngeal carcinoma choroidal metastases. Med Pediatr Oncol 2001;37:484. Apte RS, Dibernardo C, Pearlman JR, et al. Retinal metastasis presenting as a retinal hemorrhage in a patient with adenocarcinoma of the cecum. Arch Ophthalmol 2005;123: 850–853. Parsons JT, Bova FJ, Mendenhall WM, et al. Response of the normal eye to high dose radiotherapy. Oncology 1996;10: 837–848, 851–852.
Purpose: To report an unusual case of nasopharyngeal carcinoma (NPC) metastatic to the lungs and retina. To our knowledge, this is the first report of retinal metastasis from NPC. Design: Observational case report. Methods: We studied the case of a 15-year-old boy who had been recently diagnosed with metastatic NPC and was referred for evaluation of a suspicious retinal lesion in the right eye. Results: Clinical examination and fundus photography showed an amelanotic, 1-diskarea infiltration in the retina along the inferotemporal arcade that was suggestive of metastatic disease. The lesion was small and irregularly shaped by echographic examination, and a nodular area of retinal thickening was seen by optical coherence tomography. Pathologic analysis of lung biopsy and nasopharynx biopsy specimens revealed undifferentiated NPC. Conclusions: Retinal metastases need to be considered in the differential diagnosis of patients presenting with NPC and vision changes. RETINAL CASES & BRIEF REPORTS 3:8 –11, 2009
From Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami, Miller School of Medicine, and the Florida Lions Ocular Pathology Laboratory, Miami, Florida.
an incidence of 0.5 to 2 cases per 100,000 population. It has a bimodal age distribution, with a small peak observed in late childhood and a second peak occurring in people 50 to 60 years of age as reported by Vokes et al.3 In contrast to other epidermoid carcinomas of the head and neck, the undifferentiated type of NPC (World Health Organization type III) has a clear association with Epstein-Barr virus serology and no direct correlation with alcohol or tobacco.3,4 In contrast to other epidermoid cancers of the head and neck, NPC has a greater tendency for early metastatic spread.3–5 Metastases are usually present at the initial presentation and increase in frequency in advanced disease and in recurrent tumors. Altun et al4 reported that lymph node metastases occur in 75% to 90% of patients with NPC; distant metastases typically involve the lungs, skeleton, and liver. Ocular involvement is exceptionally rare, with only a few case reports of choroidal involvement6 – 8 and no reports of retinal involvement to our knowledge. Herein,
A
lthough metastatic carcinoma to the choroid is considered the most common intraocular neoplasm, metastases limited to the retina remain extremely rare occurrences.1 Bloch and Gartner2 described 4 cases of retinal metastasis among 230 patients with autopsy-proven carcinomas originating from various primary sites. To our knowledge, there are only a few reports of nasopharyngeal carcinoma (NPC) metastatic to the choroid and no reports in the literature documenting retinal metastasis. NPC is a squamous cell carcinoma that occurs in the epithelial lining of the nasopharynx. In the United States and Western Europe, NPC is a rare tumor with Reprint requests: Timothy G. Murray, MD, Bascom Palmer Eye Institute, PO Box 016880, Miami, FL 33101; e-mail: [email protected]
8
PEDIATRIC NPC WITH RETINAL METASTASIS
9
Fig. 1. Magnetic resonance imaging (MRI) of nasopharyngeal carcinoma. Axial MRI shows the primary nasopharyngeal carcinoma involving the left nasopharyngeal soft tissue (arrow; A). Chest computed tomography demonstrating metastatic disease in the lung (arrows; B).
we report a rare case of NPC with metastases to the retina and lungs. Case Report A 15-year-old boy was referred to the ocular oncology service for evaluation of a suspicious retinal lesion in the right eye. His medical history was significant for an undifferentiated NPC (World
Fig. 2. Color fundus photography of the right eye shows a retinal infiltrate along the inferior arcade (arrow; A) and a close-up view (arrow; B). Echographic examination demonstrating a small, irregularly shaped lesion at 7:30 posterior to the equator that measured 3.0 ⫻ 3.5 ⫻ 1.1 mm (arrow; C). Optical coherence tomography through the lesion illustrating the retinal infiltrate (arrow; D).
Health Organization type III disease), diagnosed 1 year prior, and metastatic disease to the lungs developing in the following months (Fig. 1). Best-corrected vision was 20/20 in each eye, and intraocular pressure was 17 mmHg in the right eye and 20 mmHg in the left eye. Funduscopic examination of the right eye was remarkable for an amelanotic, 1-disk-area infiltration in the retina along the inferotemporal arcade (Fig. 2, A and B) that was consistent with primary metastatic involvement. Otherwise, the macula, vessels,
10
RETINAL CASES & BRIEF REPORTSℜ
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2009
●
VOLUME 3
●
NUMBER 1
Fig. 3. Histopathologic examination of the nasopharynx biopsy specimen (A and B) discloses nests of pleomorphic basophilic cells (arrow; A: stain, hematoxylin– eosin; original magnification, ⫻100). More magnified views of the area are shown in B (arrow; original magnification, ⫻400). C and D, Histopathologic examination of the lung biopsy specimen. Epstein-Barr virus– encoded RNA immunohistochemical staining discloses positively stained tumor cells (dark blue staining; arrow) within the lung biopsy specimen (C; original magnification, ⫻400). D, Thyroid transcription factor-1 staining is negative within the tumor cells (small arrow) and positive (brown staining) within the normal lung epithelial cells (large arrowhead) (D; original magnification, ⫻200).
and periphery were unremarkable. Initial echographic examination showed a small, irregularly shaped lesion at 7:30 posterior to the equator that measured 3.0 ⫻ 3.5 ⫻ 1.1 mm (Fig. 2C). The lesion was too small to evaluate with A-scanning. No extraocular extension was detected. A nodular area of retinal thickening was seen by optical coherence tomography (Fig. 2D). Fluorescein angiography revealed lesional early hyperfluorescence, late staining, and no leakage. Results of histopathologic analysis of the nasopharynx and lung biopsy specimens were consistent with undifferentiated NPC (Fig. 3). Pleomorphic basophilic cells with hyperchromatic nuclei were detected in nests within the epithelium of the nasopharynx, and there were foci of deep invasion into the subepithelial stroma (Fig. 3, A and B). Similar basophilic cells were detected in the lung biopsy specimen (Fig. 3, C and D). Immunostaining of the lung biopsy specimen was positive for Epstein-Barr virus– encoded RNA, documenting the presence of Epstein-Barr virus antigens. The tumor cells were not reactive for thyroid transcription factor-1, a lung epithelial cell marker; however, the adjacent normal lung tissue was positive (Fig. 3D), thus suggesting evidence against primary lung carcinoma. The patient was treated with external-beam radiation therapy (2,160 cGy) and additional aggressive chemotherapeutic management. Chemotherapy initially consisted of a combination of 5-fluorouracil and cisplatin. This regimen failed, and treatment was then switched to a combination of paclitaxel and carboplatin. The latter
regimen also failed, and treatment with Capecitabine was subsequently started. After chemoradiation therapy, ophthalmoscopic examination, fundus photography, as well as echographic examination of the retinal lesion showed a decrease in both the basal dimension and the apical height. Vision remained 20/20 in both eyes. There were no other retinal or choroidal lesions.
Discussion Intraocular metastases to the retina are extremely rare.1,9 To our knowledge, there are no previous case reports in the literature documenting retinal metastasis from NPC, and there are only three reports of choroidal metastasis.6 – 8 External-beam radiation therapy was well tolerated in the management of this case and was associated with a decrease in the size of the retinal metastasis by ultrasonography. Tissue diagnosis from the retinal lesion would have been ideal; however, in this case, obtaining a tissue biopsy specimen would not have been appropriate given the child’s good vision and the following circumstances: the patient was known to have metastatic disease to other organs (lungs) and a new lesion to the
11
PEDIATRIC NPC WITH RETINAL METASTASIS
retina; the retinal lesion had a shape and density consistent with a mass lesion, ruling out gliosis, cotton-wool spots, or other masquerading lesions; and the retinal lesion was a new finding (not present at prior examinations), ruling out congenital lesions such as astrocytic hamartomas. Radiation therapy is the mainstay of treatment of most primary NPCs, with chemotherapy being used in advanced cases. Because the field of radiation is near the eyes, radiation toxicity may be a cause of decreased vision in these patients, as documented by Parsons et al.10 Retinal– choroidal metastases need to be considered as well in the differential diagnosis of patients presenting with NPC and vision changes. Key words: nasopharyngeal carcinoma, retinal metastasis, squamous cell carcinoma. References 1.
Pelzek CD, Schachat AP. Retinal metastases. In: Ryan SJ, ed. Retina. St. Louis, MO: Mosby; 2001:608–616.
2. 3. 4.
5.
6.
7. 8.
9.
10.
Bloch RS, Gartner S. The incidence of ocular metastatic carcinoma. Arch Ophthalmol 1971;85:673–675. Vokes EE, Liebowitz DN, Weichselbaum RR. Nasopharyngeal carcinoma. Lancet 1997;350:1087–1091. Altun M, Fandi A, Dupuis O, et al. Undifferentiated nasopharyngeal cancer (UCNT): current diagnostic and therapeutic aspects. Int J Radiat Oncol Biol Phys 1995;32:859–877. Hsu MM, Tu SM. Nasopharyngeal carcinoma in Taiwan. Clinical manifestations and results of therapy. Cancer 1983; 52:362–368. Ozyar E, Kiratli H, Akbulut S, et al. Choroid metastasis of undifferentiated nasopharyngeal carcinoma. J Laryngol Otol 1998;112:667–669. Sham JS, Choy D. Choroid metastasis from nasopharyngeal carcinoma. Eur J Surg Oncol 1991;17:384–387. Biswal BM. Restoration of vision following combination chemotherapy of nasopharyngeal carcinoma choroidal metastases. Med Pediatr Oncol 2001;37:484. Apte RS, Dibernardo C, Pearlman JR, et al. Retinal metastasis presenting as a retinal hemorrhage in a patient with adenocarcinoma of the cecum. Arch Ophthalmol 2005;123: 850–853. Parsons JT, Bova FJ, Mendenhall WM, et al. Response of the normal eye to high dose radiotherapy. Oncology 1996;10: 837–848, 851–852.
