METASTATIC LIPOSARCOMA MASQUERADING AS AN INFLAMMATORY GRANULOMA Sachin Mehta, MD, Anita Agarwal, MD
Purpose: The purpose of this study was to report a case of retroperitoneal liposarcoma metastatic to the choroid. Methods: A case report is presented of a 67-year-old woman who presented with decreased vision from an extramacular lesion resembling an inflammatory granuloma in her left eye. The lesion showed rapid growth and was associated with extensive fibrovascular proliferation. Results: Diagnostic vitrectomy showed malignant cells in the vitreous. Histopathologic evaluation of the enucleation specimen showed metastatic, dedifferentiated liposarcoma to the choroid with retinal penetration and vitreous invasion. Conclusion: Metastatic sarcoma to the choroid is very rare. In this case, the tumor was quite aggressive and penetrated through the retina, ultimately leading to enucleation. RETINAL CASES & BRIEF REPORTS 5:18–21, 2011
vitreous cavity (Figure 1). It was unclear whether the lesion originated from the retina or choroid. It measured ;6 disk areas in size and was associated with fractional retinal detachment secondary to fibrovascular proliferation extending toward the ora serrata. There was vitreous debris but no definitive evidence of vitreous seeding. Ultrasonography showed a bilobed mass with associated fractional retinal detachment. The mass measured 10.34 3 6.87 mm in base and 4.35 mm in height (Figure 2) and had medium to high internal reflectivity. A serum Toxocara enzyme-linked immunosorbent assay antibody titer and a complete blood count with differential were obtained. The antibody titer was positive at 1.3 (normal, 0–1.2), and her differential showed 8% eosinophils (normal, 0–6%). A presumptive diagnosis of Toxocara inflammatory granuloma was made, but given the peripheral location of the lesion and lack of active vitritis, a decision was made to observe without treatment. Because of personal reasons, the patient missed 2 appointments and did not present for follow-up until 7 months after her initial visit. On examination, the visual acuity in her left eye had declined to 20/400, and the lesion had doubled in size. It was associated with extensive fibrovascular proliferation, inflammatory vitreous membranes, and a fractional retinal detachment involving the majority of the temporal half of the fundus. In an attempt to slow the aggressive neovascular proliferation, 1.25 mg bevacizumab (Avastin, Genentech, South San Francisco, CA) was given off-label through infravifreal injection. A decision was made to start oral steroids and albendazole. Unfortunately, she could not tolerate oral steroids and did not obtain the albendazole. She presented 1 month later with 1/200 ‘‘E’’ visual acuity in the left eye, and the lesion appeared larger. Given the aggressive growth of the lesion, marked inflammation, and extensive fibrovascular proliferation, the possibility of an
From the Vanderbilt Eye Institute, Nashville, Tennessee.
M
etastatic carcinoma to the choroid is the most common intraocular malignancy,1 accounting for ;50% of all metastatic diseases of the eye.2 However, metastatic sarcoma to the choroid is exceedingly rare with only six reported cases in the literature.3-8 To our knowledge, retroperitoneal liposarcoma metastatic to the choroid has not been previously described. Case Report A 67-year-old woman presented with progressive blurring of vision for ;8 months after cataract surgery in her left eye. She also had occasional nausea and vomiting but did not have any other constitutional symptoms. Ophthalmologic examination showed a best-corrected visual acuity of 20/20 in the right eye and 20/50 in the left eye. There was no relative afferent pupillary defect. Intraocular pressures were 16 mm in the right eye and 13 mm in the left eye. Slit-lamp examination was notable for pseudophakia in both eyes but no evidence of active inflammation in either eye. Dilated fundus examination of the right eye was unremarkable except for signs of mild hypertensive retinopathy. In the left eye, there was a white, bilobed, solid mass located just posterior to the equator in the superotemporal quadrant and projecting into the The authors do not have any proprietary interest in the subject matter presented in this report. Reprint requests: Anita Agarwal, MD, 2311 Pierce Avenue, Nashville, TN 37232; e-mail: [email protected]
18
METASTATIC LIPOSARCOMA TO THE CHOROID
19
Fig. 1. Montage fundus photographs of the left eye. Left, Initial presentation and (Right) 7 months after initial presentation. The mass doubled in size. Note the associated aggressive fibrovascular response and the extension of the fractional detachment.
intraocular neoplasm was entertained. On further history, the patient stated that she had been diagnosed with stage 4 retroperitoneal liposarcoma in 1997, ;11 years before presentation. The dedifferentiated liposarcoma had encased her left kidney, and she ultimately required nephrectomy with postoperative chemotherapy and radiation. She had also undergone sigmoid colectomy with excision of a pelvic metastasis and radio frequency ablation of a paraspinal metastasis, both in 2006. A decision was made to perform a vitrectomy to biopsy the mass and attempt to excise it. With a magnified, stereoscopic view through a contact lens, the lesion appeared to originate from the choroid and penetrate through the retina and into the subhyaloid space. By using intraocular scissors, a triangular piece of tissue was excised from the apex and sent for pathology. The consistency of the mass was rubbery, and it was a challenge to cut into it. An attempt was made to trim it with the vitreous cutter, but it could not be engaged. After the vitreous traction had been relieved from the mass, it suddenly and completely retracted into the subretinal space. Access to the mass became extremely challenging, and
Fig. 2. B-scan ultrasonography (probe orientation: 2-o’clock position, longitudinal axis) shows projection of the tumor into the vitreous cavity with associated retinal detachment. The posterior hyaloid is hyperechogenic and is attached to the mass. Several areas of vitreous debris are present.
a decision was made to leave the remainder of it, close the eye, and await the pathology results. The vitreous specimen was negative for Toxocara antibodies by enzyme-linked immunosorbent assay testing. However, cytologic examination of the vitreous showed the presence of undifferentiated, anaplastic cells with markedly atypical nuclei and a high nuclear-to-cytoplasmic ratio (Figure 3). The pathologist confirmed that the cells appeared similar to the malignant cells in the patient’s previously excised retroperitoneal liposarcoma. Immunocytochemical studies showed focal cytokeratin expression but no S-100 expression. The biopsy from the mass was reported as a minute fragment of fibrous tissue with mildly atypical mesenchymal cells, but no definite tumor cells were visualized. In the postoperative period, the patient experienced moderate pain and retained only light perception vision. Given her poor visual prognosis and the likelihood of intraocular malignancy, she was advised to undergo enucleation. This was performed 9 days later. Histopathologic analysis showed a metastatic, pleomorphic sarcoma to the choroid that had broken through Bruch membrane and penetrated through the retina and into the vitreous cavity (Figure 4, left). The mass was fragmented with the largest fragment
Fig. 3. Cytology of the vitreous aspirate showing an enlarged, undifferentiated cell with a markedly atypical nucleus and a high nuclear-to-cytoplasmic ratio. Note the surrounding inflammatory cells.
20
RETINAL CASES & BRIEF REPORTS´ 2011 VOLUME 5 NUMBER 1
Fig. 4. Histopathology from the enucleation specimen stained with hematoxylin and eosin. Left, 53 magnification photograph shows the large tumor obliterating the normal choroidal architecture. A separate tumor fragment (*) is surrounded by erythrocytes. The overlying retina (arrow) is detached and displays outer layer atrophy and gliosis. Right, 1003 magnification photograph of the tumor fragment shows pleomorphic cells, many with hyperchromatic nuclei, prominent nucleoli, and scant cytoplasm. The tumor cells are surrounded by abundant collagen.
measuring 6 3 4 mm. The tumor consisted of pleomorphic tumor cells and abundant collagen. The cells had a high nuclear-tocytoplasmic ratio with hyperchromatic nuclei and prominent nucleoli (Figure 4, right). The choroid contained a chronic inflammatory cell infiltrate in the area surrounding the mass. The retina displayed outer layer atrophy and gliosis overlying the base of the lesion (Figure 4, left, arrow). There was no evidence of scleral or optic nerve invasion. A postoperative physical examination showed recurrence of the paraspinal metastasis, which measured 8 3 6 cm. Per her oncologist, the patient has ‘‘a metastatic process that there is no known systemic therapy for.’’ He believes additional chemotherapy is unwarranted at this time. Unfortunately, her severe renal insufficiency has precluded her from being a candidate for any investigational trials.
Discussion Sarcomas are malignant tumors of mesenchymal origin. They are relatively uncommon, representing ,1% of all new cancer cases in the United States each year.9 Sarcomas typically metastasize through the hematogenous route. The most common sites of metastasis of visceral sarcomas include the liver and lung, but metastasis to the eye is quite uncommon. Of the six reported cases of choroidal metastasis of sarcoma, primary tumors have included alveolar soft-part sarcoma of the right lower extremity,3 congenital fibrosarcoma of the left lower extremity,4 osteogenic sarcoma of the left lower extremity,5 gastrointestinal stromal tumor,6 and Ewing sarcoma of the pelvis7 and rib.8 Our patient’s primary tumor was a dedifferentiated liposarcoma, the most common type of sarcoma arising in the retroperitoneum.10 The primary tumor had encased the left kidney, and two other sites of metastatic disease had been identified and treated before the identification of the choroidal metastasis. Once the tumor cells were able to infiltrate the choroid and penetrate through the retina, a marked
fibrovascular and inflammatory response within these tissues ensued. This may have occurred as a result of secretion of vasoproliferative and inflammatory mediators by the tumor itself. Tumor penetration through the retina and into the subhyaloid space was a unique feature of this case and showed the aggressive nature of the neoplasm. Ultimately, despite attempted surgical intervention, the eye was felt to be unsalvageable, and enucleation was recommended. Other potential etiologies initially considered were Toxocara granuloma and fungal endophthalmitis. Interestingly, the presence of a positive Toxocara antibody titer and a mild serum eosinophilia initially supported the diagnosis of ocular toxocariasis. However, the rather rapid growth of the lesion in combination with the massive fibrovascular proliferation associated with it suggested a more aggressive process. This led to the decision to obtain a biopsy of the lesion and a vitreous aspirate for cytologic and Toxocara antibody testing. The vitreous cells bore a similar structural and morphologic appearance to the retroperitoneal sarcoma cells. The final diagnosis of metastatic sarcoma to the choroid with retinal invasion was confirmed by the enucleation specimen. In summary, we present a dedifferentiated retroperitoneal liposarcoma metastatic to the choroid and extending into the vitreous cavity, ultimately requiring enucleation. To our knowledge, this is the first report of such a case. Key words: choroid, granuloma, metastasis, sarcoma, tumor, eye. Acknowledgments We thank Dr. Hans Grossniklaus of the Emory Eye Center for help with pathologic confirmation and illustrations.
METASTATIC LIPOSARCOMA TO THE CHOROID
References 1. Ferry AP, Font RL. Carcinoma metastatic to the eye and orbit. I. A clinicopathologic study of 227 cases. Arch Ophthalmol 1974;92:276–286. 2. Ferry AP. Metastatic carcinoma of the eye and ocular adnexa. Int Ophthalmol Clin 1967;7:615–658. 3. Pak W, Glasgow BJ, Brown HH, Foos RY. Intraocular metastasis of alveolar soft-part sarcoma. Case report. Arch Ophthalmol 1987;105:894–895. 4. Rootman J, Carvounis EP, Dolman CL, Dimmick JE. Congenital fibrosarcoma metastatic to the choroid. Am J Ophthalmol 1979;87:632–638. 5. Spaulding AG, Woodfin MC Jr. Osteogenic sarcoma metastatic to the choroid. Arch Ophthalmol 1968;80:84–86.
21 6. Gentile CM, Lombardi AA, Croxatto JO. Choroidal metastasis from gastrointestinal stromal tumour: a case report. Br J Ophthalmol 2008;92:156–157. 7. Chan CC, Pack S, Pak E, Tsogos M, Zhuang Z. Translocation of chromosomes 11 and 22 in choroidal metastatic Ewing sarcoma detected by fluorescent in situ hybridization. Am J Ophthalmol 1999;127:226–228. 8. Jampol LM, Cottle E, Fischer DS, Albert DM. Metastasis of Ewing’s sarcoma to the choroid. Arch Ophthalmol 1973;89: 207–209. 9. Ries LAG, Harkins D, Krapcho M, et al, eds. SEER Cancer Statistics Review, 1975–2003. Bethesda, MD: National Cancer Institute; 2006. 10. Chouairy CJ, Abdul-Karim FW, MacLennan GT. Retroperitoneal liposarcoma. J Urol 2007;177:1145.
Purpose: The purpose of this study was to report a case of retroperitoneal liposarcoma metastatic to the choroid. Methods: A case report is presented of a 67-year-old woman who presented with decreased vision from an extramacular lesion resembling an inflammatory granuloma in her left eye. The lesion showed rapid growth and was associated with extensive fibrovascular proliferation. Results: Diagnostic vitrectomy showed malignant cells in the vitreous. Histopathologic evaluation of the enucleation specimen showed metastatic, dedifferentiated liposarcoma to the choroid with retinal penetration and vitreous invasion. Conclusion: Metastatic sarcoma to the choroid is very rare. In this case, the tumor was quite aggressive and penetrated through the retina, ultimately leading to enucleation. RETINAL CASES & BRIEF REPORTS 5:18–21, 2011
vitreous cavity (Figure 1). It was unclear whether the lesion originated from the retina or choroid. It measured ;6 disk areas in size and was associated with fractional retinal detachment secondary to fibrovascular proliferation extending toward the ora serrata. There was vitreous debris but no definitive evidence of vitreous seeding. Ultrasonography showed a bilobed mass with associated fractional retinal detachment. The mass measured 10.34 3 6.87 mm in base and 4.35 mm in height (Figure 2) and had medium to high internal reflectivity. A serum Toxocara enzyme-linked immunosorbent assay antibody titer and a complete blood count with differential were obtained. The antibody titer was positive at 1.3 (normal, 0–1.2), and her differential showed 8% eosinophils (normal, 0–6%). A presumptive diagnosis of Toxocara inflammatory granuloma was made, but given the peripheral location of the lesion and lack of active vitritis, a decision was made to observe without treatment. Because of personal reasons, the patient missed 2 appointments and did not present for follow-up until 7 months after her initial visit. On examination, the visual acuity in her left eye had declined to 20/400, and the lesion had doubled in size. It was associated with extensive fibrovascular proliferation, inflammatory vitreous membranes, and a fractional retinal detachment involving the majority of the temporal half of the fundus. In an attempt to slow the aggressive neovascular proliferation, 1.25 mg bevacizumab (Avastin, Genentech, South San Francisco, CA) was given off-label through infravifreal injection. A decision was made to start oral steroids and albendazole. Unfortunately, she could not tolerate oral steroids and did not obtain the albendazole. She presented 1 month later with 1/200 ‘‘E’’ visual acuity in the left eye, and the lesion appeared larger. Given the aggressive growth of the lesion, marked inflammation, and extensive fibrovascular proliferation, the possibility of an
From the Vanderbilt Eye Institute, Nashville, Tennessee.
M
etastatic carcinoma to the choroid is the most common intraocular malignancy,1 accounting for ;50% of all metastatic diseases of the eye.2 However, metastatic sarcoma to the choroid is exceedingly rare with only six reported cases in the literature.3-8 To our knowledge, retroperitoneal liposarcoma metastatic to the choroid has not been previously described. Case Report A 67-year-old woman presented with progressive blurring of vision for ;8 months after cataract surgery in her left eye. She also had occasional nausea and vomiting but did not have any other constitutional symptoms. Ophthalmologic examination showed a best-corrected visual acuity of 20/20 in the right eye and 20/50 in the left eye. There was no relative afferent pupillary defect. Intraocular pressures were 16 mm in the right eye and 13 mm in the left eye. Slit-lamp examination was notable for pseudophakia in both eyes but no evidence of active inflammation in either eye. Dilated fundus examination of the right eye was unremarkable except for signs of mild hypertensive retinopathy. In the left eye, there was a white, bilobed, solid mass located just posterior to the equator in the superotemporal quadrant and projecting into the The authors do not have any proprietary interest in the subject matter presented in this report. Reprint requests: Anita Agarwal, MD, 2311 Pierce Avenue, Nashville, TN 37232; e-mail: [email protected]
18
METASTATIC LIPOSARCOMA TO THE CHOROID
19
Fig. 1. Montage fundus photographs of the left eye. Left, Initial presentation and (Right) 7 months after initial presentation. The mass doubled in size. Note the associated aggressive fibrovascular response and the extension of the fractional detachment.
intraocular neoplasm was entertained. On further history, the patient stated that she had been diagnosed with stage 4 retroperitoneal liposarcoma in 1997, ;11 years before presentation. The dedifferentiated liposarcoma had encased her left kidney, and she ultimately required nephrectomy with postoperative chemotherapy and radiation. She had also undergone sigmoid colectomy with excision of a pelvic metastasis and radio frequency ablation of a paraspinal metastasis, both in 2006. A decision was made to perform a vitrectomy to biopsy the mass and attempt to excise it. With a magnified, stereoscopic view through a contact lens, the lesion appeared to originate from the choroid and penetrate through the retina and into the subhyaloid space. By using intraocular scissors, a triangular piece of tissue was excised from the apex and sent for pathology. The consistency of the mass was rubbery, and it was a challenge to cut into it. An attempt was made to trim it with the vitreous cutter, but it could not be engaged. After the vitreous traction had been relieved from the mass, it suddenly and completely retracted into the subretinal space. Access to the mass became extremely challenging, and
Fig. 2. B-scan ultrasonography (probe orientation: 2-o’clock position, longitudinal axis) shows projection of the tumor into the vitreous cavity with associated retinal detachment. The posterior hyaloid is hyperechogenic and is attached to the mass. Several areas of vitreous debris are present.
a decision was made to leave the remainder of it, close the eye, and await the pathology results. The vitreous specimen was negative for Toxocara antibodies by enzyme-linked immunosorbent assay testing. However, cytologic examination of the vitreous showed the presence of undifferentiated, anaplastic cells with markedly atypical nuclei and a high nuclear-to-cytoplasmic ratio (Figure 3). The pathologist confirmed that the cells appeared similar to the malignant cells in the patient’s previously excised retroperitoneal liposarcoma. Immunocytochemical studies showed focal cytokeratin expression but no S-100 expression. The biopsy from the mass was reported as a minute fragment of fibrous tissue with mildly atypical mesenchymal cells, but no definite tumor cells were visualized. In the postoperative period, the patient experienced moderate pain and retained only light perception vision. Given her poor visual prognosis and the likelihood of intraocular malignancy, she was advised to undergo enucleation. This was performed 9 days later. Histopathologic analysis showed a metastatic, pleomorphic sarcoma to the choroid that had broken through Bruch membrane and penetrated through the retina and into the vitreous cavity (Figure 4, left). The mass was fragmented with the largest fragment
Fig. 3. Cytology of the vitreous aspirate showing an enlarged, undifferentiated cell with a markedly atypical nucleus and a high nuclear-to-cytoplasmic ratio. Note the surrounding inflammatory cells.
20
RETINAL CASES & BRIEF REPORTS´ 2011 VOLUME 5 NUMBER 1
Fig. 4. Histopathology from the enucleation specimen stained with hematoxylin and eosin. Left, 53 magnification photograph shows the large tumor obliterating the normal choroidal architecture. A separate tumor fragment (*) is surrounded by erythrocytes. The overlying retina (arrow) is detached and displays outer layer atrophy and gliosis. Right, 1003 magnification photograph of the tumor fragment shows pleomorphic cells, many with hyperchromatic nuclei, prominent nucleoli, and scant cytoplasm. The tumor cells are surrounded by abundant collagen.
measuring 6 3 4 mm. The tumor consisted of pleomorphic tumor cells and abundant collagen. The cells had a high nuclear-tocytoplasmic ratio with hyperchromatic nuclei and prominent nucleoli (Figure 4, right). The choroid contained a chronic inflammatory cell infiltrate in the area surrounding the mass. The retina displayed outer layer atrophy and gliosis overlying the base of the lesion (Figure 4, left, arrow). There was no evidence of scleral or optic nerve invasion. A postoperative physical examination showed recurrence of the paraspinal metastasis, which measured 8 3 6 cm. Per her oncologist, the patient has ‘‘a metastatic process that there is no known systemic therapy for.’’ He believes additional chemotherapy is unwarranted at this time. Unfortunately, her severe renal insufficiency has precluded her from being a candidate for any investigational trials.
Discussion Sarcomas are malignant tumors of mesenchymal origin. They are relatively uncommon, representing ,1% of all new cancer cases in the United States each year.9 Sarcomas typically metastasize through the hematogenous route. The most common sites of metastasis of visceral sarcomas include the liver and lung, but metastasis to the eye is quite uncommon. Of the six reported cases of choroidal metastasis of sarcoma, primary tumors have included alveolar soft-part sarcoma of the right lower extremity,3 congenital fibrosarcoma of the left lower extremity,4 osteogenic sarcoma of the left lower extremity,5 gastrointestinal stromal tumor,6 and Ewing sarcoma of the pelvis7 and rib.8 Our patient’s primary tumor was a dedifferentiated liposarcoma, the most common type of sarcoma arising in the retroperitoneum.10 The primary tumor had encased the left kidney, and two other sites of metastatic disease had been identified and treated before the identification of the choroidal metastasis. Once the tumor cells were able to infiltrate the choroid and penetrate through the retina, a marked
fibrovascular and inflammatory response within these tissues ensued. This may have occurred as a result of secretion of vasoproliferative and inflammatory mediators by the tumor itself. Tumor penetration through the retina and into the subhyaloid space was a unique feature of this case and showed the aggressive nature of the neoplasm. Ultimately, despite attempted surgical intervention, the eye was felt to be unsalvageable, and enucleation was recommended. Other potential etiologies initially considered were Toxocara granuloma and fungal endophthalmitis. Interestingly, the presence of a positive Toxocara antibody titer and a mild serum eosinophilia initially supported the diagnosis of ocular toxocariasis. However, the rather rapid growth of the lesion in combination with the massive fibrovascular proliferation associated with it suggested a more aggressive process. This led to the decision to obtain a biopsy of the lesion and a vitreous aspirate for cytologic and Toxocara antibody testing. The vitreous cells bore a similar structural and morphologic appearance to the retroperitoneal sarcoma cells. The final diagnosis of metastatic sarcoma to the choroid with retinal invasion was confirmed by the enucleation specimen. In summary, we present a dedifferentiated retroperitoneal liposarcoma metastatic to the choroid and extending into the vitreous cavity, ultimately requiring enucleation. To our knowledge, this is the first report of such a case. Key words: choroid, granuloma, metastasis, sarcoma, tumor, eye. Acknowledgments We thank Dr. Hans Grossniklaus of the Emory Eye Center for help with pathologic confirmation and illustrations.
METASTATIC LIPOSARCOMA TO THE CHOROID
References 1. Ferry AP, Font RL. Carcinoma metastatic to the eye and orbit. I. A clinicopathologic study of 227 cases. Arch Ophthalmol 1974;92:276–286. 2. Ferry AP. Metastatic carcinoma of the eye and ocular adnexa. Int Ophthalmol Clin 1967;7:615–658. 3. Pak W, Glasgow BJ, Brown HH, Foos RY. Intraocular metastasis of alveolar soft-part sarcoma. Case report. Arch Ophthalmol 1987;105:894–895. 4. Rootman J, Carvounis EP, Dolman CL, Dimmick JE. Congenital fibrosarcoma metastatic to the choroid. Am J Ophthalmol 1979;87:632–638. 5. Spaulding AG, Woodfin MC Jr. Osteogenic sarcoma metastatic to the choroid. Arch Ophthalmol 1968;80:84–86.
21 6. Gentile CM, Lombardi AA, Croxatto JO. Choroidal metastasis from gastrointestinal stromal tumour: a case report. Br J Ophthalmol 2008;92:156–157. 7. Chan CC, Pack S, Pak E, Tsogos M, Zhuang Z. Translocation of chromosomes 11 and 22 in choroidal metastatic Ewing sarcoma detected by fluorescent in situ hybridization. Am J Ophthalmol 1999;127:226–228. 8. Jampol LM, Cottle E, Fischer DS, Albert DM. Metastasis of Ewing’s sarcoma to the choroid. Arch Ophthalmol 1973;89: 207–209. 9. Ries LAG, Harkins D, Krapcho M, et al, eds. SEER Cancer Statistics Review, 1975–2003. Bethesda, MD: National Cancer Institute; 2006. 10. Chouairy CJ, Abdul-Karim FW, MacLennan GT. Retroperitoneal liposarcoma. J Urol 2007;177:1145.
