PARTIAL REGRESSION OF VITREORETINAL LYMPHOMA AFTER FINE NEEDLE ASPIRATION BIOPSY Gregory L. Fenton, MD,* Carol L. Shields, MD,* Noel Horgan, MD,* Brian P. Marr, MD,* Hormoz Ehya, MD,† Jerry A. Shields, MD*
Purpose: To report a case of regression of vitreoretinal lymphoma after fine-needle aspiration biopsy. Methods: Interventional case report. Results: A 72-year-old woman with a history of systemic non-Hodgkin lymphoma noted difficulty focusing with the right eye and was found to have multiple yellow sub–retinal pigment epithelium (sub-RPE) infliltrates. Fine-needle aspiration biopsy disclosed large atypical lymphocytes consistent with large-cell lymphoma. Four weeks after biopsy, the sub-RPE lesions resolved without additional treatment. Three months later, the tumors recurred. The patient received systemic chemotherapy, and her condition remained stable without brain involvement at the 2-year follow-up. Conclusion: Fine-needle aspiration biopsy can induce temporary regression of vitreoretinal lymphoma. Patients with vitreoretinal lymphoma should have regular systemic follow-up examinations due to the risk of central nervous system recurrence. RETINAL CASES & BRIEF REPORTS 2:163–165, 2008
Case Report
From the *Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia; and the †Department of Pathology, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
A 72-year-old woman noted difficulty focusing with her right eye over 3 weeks. She had a history of chemotherapy-treated abdominal non-Hodgkin’s large cell lymphoma (LCL) and a history of primary breast carcinoma treated with lumpectomy, radiotherapy, and tamoxifen. Visual acuity was 20/30 in each eye. The left eye was normal. The right eye showed fine anterior vitreous cells and approximately 30 extramacular, yellow, subretinal pigment epithelial (sub-RPE) infiltrates, consistent with vitreoretinal lymphoma (Figure 1). The largest sub-RPE lesion was sampled by transvitreal FNAB. The aspirate was processed by a cytocentrifuge technique and the alcohol-fixed preparations were stained by the Papanicolaou method (Figure 2). The specimen was moderately cellular, but a majority of the cells were necrotic. The viable cells were single and round, possessing large nuclei and scant cytoplasm. The cells exhibited coarse chromatin and irregular nuclear membrane. Prominent nucleoli were evident in some cells. A limited panel of immunocytochemical stains showed positive staining of the cells for leukocyte common antigen (CD45) and negative staining for cytokeratin. A diagnosis of large cell lymphoma was made on the basis of morphology and immunophenotype. Four weeks after FNAB, with no intervening treatment, there was complete resolution of most of the sub-RPE infiltrates, even though only one had been biopsied (Figure 3, A and B). There was no evidence of brain or systemic lymphoma by cerebrospinal fluid (CSF) analysis or imaging studies. Spontaneous regression of subRPE lymphoma was diagnosed and close monitoring was advised.
S
pontaneous regression of cancer is defined as the complete or partial disappearance of a malignant tumor in the absence of treatment.1 Although rare, spontaneous regression of uveal metastases2 and of primary choroidal melanoma3 have been reported. We report a case of spontaneous regression of vitreoretinal lymphoma that occurred following fine needle aspiration biopsy (FNAB). Support provided by the Eye Tumor Research Foundation, Philadelphia, Pennsylvania (C.L.S., J.A.S.); the Retina Research Foundation of the Retina Society, Capetown, South Africa (C.L.S.); Mellon Charitable Giving from the Martha W. Rogers Charitable Trust, Philadelphia, Pennsylvania (C.L.S.); the Paul Kayser International Award of Merit in Retina Research, Houston, Texas (J.A.S.); and a donation from Michael, Bruce, and Ellen Ratner, New York, New York (J.A.S., C.L.S.). No author has any proprietary interest. Reprint requests: Carol L. Shields, MD, Ocular Oncology Service, Suite 1440, Wills Eye Hospital, 840 Walnut Street, Philadelphia, PA 19107; e-mail: [email protected]
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Fig. 2. Cytopathology of the fine needle aspiration biopsy specimen demonstrated large atypical lymphoid cells in a background of necrotic cells (Papanicolaou stain). Inset: Immunohistochemical stain showing positive staining for leukocyte common antigen (CD45).
Fig. 1. Wide angle fundus photograph of the right eye showed multiple yellow subretinal pigment epithelial infiltrates consistent with vitreoretinal lymphoma. The largest infiltrate, temporal to the fovea, was biopsied using fine needle aspiration.
Three months later, the sub-RPE infiltrates recurred. The yellow infiltrates ranged in diameter from 0.3 mm to 3.0 mm, and numbered approximately 20. Systemic chemotherapy was administered (six cycles of vincristine, Adriamycin, bleomycin, and rituxan; seven cycles of methotrexate). As CSF analysis remained normal, intrathecal chemotherapy was not administered. The tumors regressed, and the patient remains stable without evidence of systemic or brain involvement at 2-year follow-up.
Discussion Intraocular lymphoma presents as two somewhat distinct entities, the uveal and the vitreoretinal forms. The uveal form is associated with systemic nonHodgkin’s lymphoma. The vitreoretinal form is associated with brain lymphoma and can involve the ret-
ina, vitreous, sub-RPE, and optic nerve, and carries a worse prognosis. Spontaneous regression of cancer is extremely rare, and its occurrence does not necessarily imply a cure. It has been estimated that up to 15–30% of cutaneous melanoma4 and 13–23% of low-grade lymphomas5 demonstrate spontaneous regression. The incidence of recurrence after spontaneous regression is variable. Al-Yamany and coworkers found relapse of primary brain lymphoma 1, 2, and 4 years following initial spontaneous regression in 3 cases.6 Our case showed spontaneous regression of LCL within 1 month of FNAB, but recurrence was noted 3 months later. Similarly, Goto and coworkers have reported spontaneous regression of intraocular lymphoma following biopsy without recurrence at 1-year follow-up.7 Patients with vitreoretinal lymphoma should, however, have regular systemic follow-up to
Fig. 3. Inferonasal fundus showing regression of subretinal pigment epithelial (sub-RPE) infiltrates. Note that the needle biopsy was performed temporally and not at this site. A, Before biopsy, the sub-RPE infiltrates were visible. B, Same area of fundus 1 month after biopsy. Note that the sub-RPE infiltrate has resolved, leaving only RPE mottling.
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monitor for recurrence within the central nervous system. Spontaneous regression of cancer can portend a worse prognosis.8 In a study of 486 patients with cutaneous melanoma, 10-year survival decreased from 95% to 79% in those with previous spontaneous regression.4 Spontaneous regression of choroidal metastases from renal cell carcinoma and cutaneous melanoma has also been associated with worse prognosis.2,9 The speculated mechanisms for spontaneous regression of cancers involve host immune defenses, tumor necrosis or vascular insufficiency, infection, hormonal mechanisms, apoptosis, psychological factors, and others.1,5 In this case, needle biopsy might have altered the immune status of the globe and temporarily caused tumor regression. We have not previously witnessed this finding in over 500 intraocular FNABs.10 References 1.
2.
Challis GB, Stam HJ. The spontaneous regression of cancer: a review of cases from 1900 to 1987. Acta Oncologica 1990;29:545–549. Shields CL, Piccone MR, Fung KL, Shields JA. Spontaneous
3.
4.
5. 6.
7.
8.
9.
10.
regression of metastatic cutaneous melanoma to the choroid. Retina 2002;22:806–808. Shields CL, Shields JA, Santos CM, et al. Incomplete spontaneous regression of choroidal melanoma associated with inflammation. Arch Ophthalmol 1999;117:1245–1247. Sondergaard K, Hou-Jensen K. Partial regression in thin primary cutaneous malignant melanomas clinical stage I. Virchows Arch 1985;408:241–247. Papac RJ. Spontaneous regression of cancer. Cancer Treatment Reviews 1996;22:395–423. Al-Yamany M, Lozano A, Nag S, et al. Spontaneous remission of primary central nervous system lymphoma: report of three cases and discussion of pathophysiology. J NeuroOncol 1999;42:151–159. Goto H, Murase K, Usui M. Case of spontaneous regression of intraocular lymphoma demonstrated by subretinal biopsy [Japanese]. Nippon Ganka Gakkai Zasshi Acta Societatis Ophthalmologicae Japonicae 2006;110:226–231. Ronan SG, Eng AM, Briele HA, et al. Thin malignant melanomas with regression and metastases. Arch. Dermatol 1987;23:1326–1330. Hammad AM, Paris GR, van Heuven WAJ, et al. Spontaneous regression of choroidal metastasis from renal cell carcinoma. Am J Ophthalmol 2003;135:911–913. Shields JA, Shields CL, Ehya H, et al. Fine needle aspiration biopsy of suspected intraocular tumors. The 1992 Urwick Lecture. Ophthalmology 1993;100:1677–1684.
Purpose: To report a case of regression of vitreoretinal lymphoma after fine-needle aspiration biopsy. Methods: Interventional case report. Results: A 72-year-old woman with a history of systemic non-Hodgkin lymphoma noted difficulty focusing with the right eye and was found to have multiple yellow sub–retinal pigment epithelium (sub-RPE) infliltrates. Fine-needle aspiration biopsy disclosed large atypical lymphocytes consistent with large-cell lymphoma. Four weeks after biopsy, the sub-RPE lesions resolved without additional treatment. Three months later, the tumors recurred. The patient received systemic chemotherapy, and her condition remained stable without brain involvement at the 2-year follow-up. Conclusion: Fine-needle aspiration biopsy can induce temporary regression of vitreoretinal lymphoma. Patients with vitreoretinal lymphoma should have regular systemic follow-up examinations due to the risk of central nervous system recurrence. RETINAL CASES & BRIEF REPORTS 2:163–165, 2008
Case Report
From the *Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia; and the †Department of Pathology, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
A 72-year-old woman noted difficulty focusing with her right eye over 3 weeks. She had a history of chemotherapy-treated abdominal non-Hodgkin’s large cell lymphoma (LCL) and a history of primary breast carcinoma treated with lumpectomy, radiotherapy, and tamoxifen. Visual acuity was 20/30 in each eye. The left eye was normal. The right eye showed fine anterior vitreous cells and approximately 30 extramacular, yellow, subretinal pigment epithelial (sub-RPE) infiltrates, consistent with vitreoretinal lymphoma (Figure 1). The largest sub-RPE lesion was sampled by transvitreal FNAB. The aspirate was processed by a cytocentrifuge technique and the alcohol-fixed preparations were stained by the Papanicolaou method (Figure 2). The specimen was moderately cellular, but a majority of the cells were necrotic. The viable cells were single and round, possessing large nuclei and scant cytoplasm. The cells exhibited coarse chromatin and irregular nuclear membrane. Prominent nucleoli were evident in some cells. A limited panel of immunocytochemical stains showed positive staining of the cells for leukocyte common antigen (CD45) and negative staining for cytokeratin. A diagnosis of large cell lymphoma was made on the basis of morphology and immunophenotype. Four weeks after FNAB, with no intervening treatment, there was complete resolution of most of the sub-RPE infiltrates, even though only one had been biopsied (Figure 3, A and B). There was no evidence of brain or systemic lymphoma by cerebrospinal fluid (CSF) analysis or imaging studies. Spontaneous regression of subRPE lymphoma was diagnosed and close monitoring was advised.
S
pontaneous regression of cancer is defined as the complete or partial disappearance of a malignant tumor in the absence of treatment.1 Although rare, spontaneous regression of uveal metastases2 and of primary choroidal melanoma3 have been reported. We report a case of spontaneous regression of vitreoretinal lymphoma that occurred following fine needle aspiration biopsy (FNAB). Support provided by the Eye Tumor Research Foundation, Philadelphia, Pennsylvania (C.L.S., J.A.S.); the Retina Research Foundation of the Retina Society, Capetown, South Africa (C.L.S.); Mellon Charitable Giving from the Martha W. Rogers Charitable Trust, Philadelphia, Pennsylvania (C.L.S.); the Paul Kayser International Award of Merit in Retina Research, Houston, Texas (J.A.S.); and a donation from Michael, Bruce, and Ellen Ratner, New York, New York (J.A.S., C.L.S.). No author has any proprietary interest. Reprint requests: Carol L. Shields, MD, Ocular Oncology Service, Suite 1440, Wills Eye Hospital, 840 Walnut Street, Philadelphia, PA 19107; e-mail: [email protected]
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Fig. 2. Cytopathology of the fine needle aspiration biopsy specimen demonstrated large atypical lymphoid cells in a background of necrotic cells (Papanicolaou stain). Inset: Immunohistochemical stain showing positive staining for leukocyte common antigen (CD45).
Fig. 1. Wide angle fundus photograph of the right eye showed multiple yellow subretinal pigment epithelial infiltrates consistent with vitreoretinal lymphoma. The largest infiltrate, temporal to the fovea, was biopsied using fine needle aspiration.
Three months later, the sub-RPE infiltrates recurred. The yellow infiltrates ranged in diameter from 0.3 mm to 3.0 mm, and numbered approximately 20. Systemic chemotherapy was administered (six cycles of vincristine, Adriamycin, bleomycin, and rituxan; seven cycles of methotrexate). As CSF analysis remained normal, intrathecal chemotherapy was not administered. The tumors regressed, and the patient remains stable without evidence of systemic or brain involvement at 2-year follow-up.
Discussion Intraocular lymphoma presents as two somewhat distinct entities, the uveal and the vitreoretinal forms. The uveal form is associated with systemic nonHodgkin’s lymphoma. The vitreoretinal form is associated with brain lymphoma and can involve the ret-
ina, vitreous, sub-RPE, and optic nerve, and carries a worse prognosis. Spontaneous regression of cancer is extremely rare, and its occurrence does not necessarily imply a cure. It has been estimated that up to 15–30% of cutaneous melanoma4 and 13–23% of low-grade lymphomas5 demonstrate spontaneous regression. The incidence of recurrence after spontaneous regression is variable. Al-Yamany and coworkers found relapse of primary brain lymphoma 1, 2, and 4 years following initial spontaneous regression in 3 cases.6 Our case showed spontaneous regression of LCL within 1 month of FNAB, but recurrence was noted 3 months later. Similarly, Goto and coworkers have reported spontaneous regression of intraocular lymphoma following biopsy without recurrence at 1-year follow-up.7 Patients with vitreoretinal lymphoma should, however, have regular systemic follow-up to
Fig. 3. Inferonasal fundus showing regression of subretinal pigment epithelial (sub-RPE) infiltrates. Note that the needle biopsy was performed temporally and not at this site. A, Before biopsy, the sub-RPE infiltrates were visible. B, Same area of fundus 1 month after biopsy. Note that the sub-RPE infiltrate has resolved, leaving only RPE mottling.
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monitor for recurrence within the central nervous system. Spontaneous regression of cancer can portend a worse prognosis.8 In a study of 486 patients with cutaneous melanoma, 10-year survival decreased from 95% to 79% in those with previous spontaneous regression.4 Spontaneous regression of choroidal metastases from renal cell carcinoma and cutaneous melanoma has also been associated with worse prognosis.2,9 The speculated mechanisms for spontaneous regression of cancers involve host immune defenses, tumor necrosis or vascular insufficiency, infection, hormonal mechanisms, apoptosis, psychological factors, and others.1,5 In this case, needle biopsy might have altered the immune status of the globe and temporarily caused tumor regression. We have not previously witnessed this finding in over 500 intraocular FNABs.10 References 1.
2.
Challis GB, Stam HJ. The spontaneous regression of cancer: a review of cases from 1900 to 1987. Acta Oncologica 1990;29:545–549. Shields CL, Piccone MR, Fung KL, Shields JA. Spontaneous
3.
4.
5. 6.
7.
8.
9.
10.
regression of metastatic cutaneous melanoma to the choroid. Retina 2002;22:806–808. Shields CL, Shields JA, Santos CM, et al. Incomplete spontaneous regression of choroidal melanoma associated with inflammation. Arch Ophthalmol 1999;117:1245–1247. Sondergaard K, Hou-Jensen K. Partial regression in thin primary cutaneous malignant melanomas clinical stage I. Virchows Arch 1985;408:241–247. Papac RJ. Spontaneous regression of cancer. Cancer Treatment Reviews 1996;22:395–423. Al-Yamany M, Lozano A, Nag S, et al. Spontaneous remission of primary central nervous system lymphoma: report of three cases and discussion of pathophysiology. J NeuroOncol 1999;42:151–159. Goto H, Murase K, Usui M. Case of spontaneous regression of intraocular lymphoma demonstrated by subretinal biopsy [Japanese]. Nippon Ganka Gakkai Zasshi Acta Societatis Ophthalmologicae Japonicae 2006;110:226–231. Ronan SG, Eng AM, Briele HA, et al. Thin malignant melanomas with regression and metastases. Arch. Dermatol 1987;23:1326–1330. Hammad AM, Paris GR, van Heuven WAJ, et al. Spontaneous regression of choroidal metastasis from renal cell carcinoma. Am J Ophthalmol 2003;135:911–913. Shields JA, Shields CL, Ehya H, et al. Fine needle aspiration biopsy of suspected intraocular tumors. The 1992 Urwick Lecture. Ophthalmology 1993;100:1677–1684.
