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Lung adenocarcinoma and malignant uveitis masquerade syndrome: author reply
Letters to the Editor
Lung Adenocarcinoma and Malignant Uveitis Masquerade Syndrome Dear Editor: We endorse Rothova’s recommendation to use a combination of cytology and immunophenotyping as a means of identifying the primary tumor in malignant uveitis masquerade syndrome. This approach led us to a diagnosis of lung adenocarcinoma in an apparently healthy 65 year old man who had smoked for 40 years and presented with progressive vitritis in his right eye. Cytology from a diagnostic vitrectomy showed nuclear hyperchromasia and pleomorphism with mitotic figures together with cellular cohesion, vacuolated cytoplasm (black arrowheads), and occasional signet ring forms (open black arrow) supporting a diagnosis of adenocarcinoma (Figure 1). The expression of keratins (AE1:AE3 and CAM 5.2) and carcinoembryonic antigen (CEA) on immunoperoxidase staining, with the lack of staining for leukocyte common antigen (CD45), vimentin and S-100 protein were compatible with carcinoma. The expression of cytokeratin 7 and thyroid transcription factor 1 (TTF-1), without expression of cytokeratin 20, suggested a pulmonary primary. Subsequent clinical assessment, chest Xray, sputum cytology, liver function tests, barium enema, and throat endoscopy were negative. Computerized tomography later confirmed the presence of a lesion in the upper lobe of the right lung primary tumor with hilar lymphadenopathy (Figure 2). Aqueous sampling prior to the CT scan had reproduced the cellular findings, highlighting the value of paracentesis as a
Figure 1. Marked nuclear hyperchromasia and pleomorphism with mitotic figures, combined with cellular cohesion, vacuolated cytoplasm (black arrowheads) and occasional signet ring forms (open black arrow) support a diagnosis of adenocarcinoma. The expression of keratins (AE1: AE3 and CAM 5.2) and carcinoembryonic antigen (CEA) on immunoperoxidase staining, with the lack of staining for leukocyte common antigen (CD45), vimentin and S-100 protein confirm a carcinoma. The expression of cytokeratin 7 and thyroid transcription factor 1 (TTF-1), without expression of cytokeratin 20, is compatible with a pulmonary primary.
Figure 2. A hyper-dense lesion in the upper lobe of the right lung in association with hilar lymphadenopathy confirms the presence of a lung primary.
less invasive diagnostic option compared with a formal vitrectomy. CHETAN K. PATEL, BSC., FRCOPHTH WAI CHING LAM, MD, FRCS(C) SCOTT BOERNER, MD, FRCP(C) Toronto, Ontario, Canada Author reply Dear Editor: Dr. Patel et al demonstrate positive cytologic findings and immunperoxidase staining of aqueous and vitreous fluids in a patient with an intraocular metastasis of lung adenocarcinoma. They highlight the possibility of diagnosing patients suspected of having intraocular malignancy by means of aqueous analysis, which was also one of the conclusions of our study. In our study of 19 patients with malignant uveitis masquerade syndrome, five of eight aqueous samples examined gave positive results, so that in these five cases a more traumatic vitrectomy was not necessary. Pars plana vitrectomy is a more aggressive diagnostic procedure and is associated with a considerable number of postoperative complications. In addition, the possibility of inducing new metastases by handling the tissues is certainly greater with vitrectomy than with transcorneal collection of aqueous fluid. It should be noted, however, that no data are available on sensitivities of aqueous and vitreous cytologic and immunophenotyping examinations in ocular malignancies. In our study, five of eight (63%) aqueous samples were positive (2 of 3 with cytology and 3 of 5 with immunophenotyping), as well as 8 of 14 (57%) vitreous samples (5 of 9 with cytology and 3 of 5 with immunophenotyping). However, no definitive conclusions can be drawn from this small number of patients with various malignancies.
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Ophthalmology Volume 108, Number 12, December 2001 It is important to note that the negative cytologic results on aqueous do not exclude the presence of intraocular malignancy, and in such cases, one should proceed with further diagnostic examinations to ascertain the definitive diagnosis. At present, the aqueous analysis might be an acceptable initial diagnostic procedure, which might in a certain percentage of patients (in our study more than 50%) preclude a more aggressive diagnostic vitrectomy. ANIKI ROTHOVA, MD, PHD Utrecht, The Netherlands
Corneal Effects of Latanoprost and Timolol Dear Editor: In the article and discussion by Lass et al on the corneal effects of latanoprost and timolol (Ophthalmology 2001; 108:264 –71), I was struck by the certainty of the statement in their discussion that “The. . .increase in. . .cell density at one year for. . . latanoprost. . . “does not represent an actual increase in cell density. . .” (my italics). Although this would seem a reasonable interpretation based on what (little) we know about the effects of this class of drugs on various tissues and about endothelial cell physiology and reproductive ability, in fact, the best that can be inferred from their presented data is that if there is a change, it falls within the “error of measurement.” Whether latanoprost has a small effect on endothelial cell density cannot be determined from the data presented. Given the somewhat unusual effects that latanoprost has been noted to have on some tissues, it would seem prudent to keep an open mind with regard to its effects on other tissues. GEORGE F. CORRENT, MD, PHD Ft. Lauderdale, Florida
Topical Ketorolac after Cataract Surgery Dear Editor: For approximately one year I have been using ketorolac as my sole anti-inflammatory in conjunction with a fluoroquinolone after cataract surgery. Thus, I was very interested in the article by Solomon et al.1 With the introduction of phaco-chop, I had seen a reduction in postoperative inflammation and corneal edema in the average patient. Topical anesthesia has yielded less postoperative discomfort than in previous cases with peri- or retrobulbar anesthesia. I have also learned that ketorolac is used widely for pain control after orthopedic cases. Additionally, I question the use of steroids in the perioperative period when the most feared complication is infection. All of these factors led me to ketorolac after phacoemulsification. Overall, I have been very pleased by the results. Postoperative discomfort is minimal and patients tolerate the burning well. Modest corneal edema clears rapidly. Anterior chamber cell and flare clear more slowly so it is important that inflammation is low from the start. While I have no hard data, CME seems less common, and when it does occur it responds quickly to the addition of topical steroids. There are certain cases in which I will always use prednisolone together with ketorolac: previous history of CME, previous history of iritis, severe corneal edema/dystrophy, severe cell and flare, and capsular rupture with/without vitrectomy. I will also start steroids if cell and flare are still significant at three to four weeks after the surgery. I feel that ketorolac is a viable alternative to steroids in uncomplicated phacoemulsification. I have no interest in nor am I employed by Allergan pharmaceuticals.
Author reply Dear Editor: Dr. Corrent has raised concern about how definitive our statement that the “. . .marginal increase in average cell density at one year for the latanoprost group and the FC group does not represent an actual increase in the cell density of these subjects. . .” I believe we both are in agreement that this slight increase in these two groups relates solely to an error of measurement in the cell density determination technique, as stated in the article. We believe that this is not due to any stimulatory effect of latanoprost or its combination on endothelial replication, given the limited potential for such replication in the normal or injured cornea. I agree with Dr. Corrent, however, that we cannot absolutely conclude this from our study, and I would therefore modify our statement from “does not” to “most likely does not.” At the same time, it is important to emphasize that there was no significant difference in the mean change in central endothelial cell density between the three groups, including the timolol group, at 1 year, and that the change was “comparable with the rate of change of approximately 0.6% cell loss annually. . .in a normally aging population.26” JONATHAN H. LASS, MD Cleveland, Ohio
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CHARLES J. KAISER, MD Miami, Florida REFERENCE 1. Solomon KD, Cheetham JK, DeGryse R, et al. Topical ketorolac tromethamine 0.5% ophthalmic solution in ocular inflammation after cataract surgery. Ophthalmology 2001;108:331–7.
Nonpenetrating Deep Sclerectomy for SturgeWeber Syndrome Dear Editor: Budenz et al1 have recently reported their results with the two-stage Baervedlt implant combined with prophylactic sclerostomies in children with late-onset glaucoma in Sturge-Weber syndrome (SWS). This surgical approach minimized the risk for choroidal effusions and hemorrhages; however, it did not eliminate it, and choroidal effusions occurred in 2 of 10 eyes (20%). We have performed a nonpenetrating deep sclerectomy with a reticulated hyaluronic acid implant in a 17-year-old patient with SWS and secondary glaucoma in the right eye. Preoperative intraocular pressure (IOP) was 30 mmHg with medical therapy, and postoperative IOP was 15 mmHg without treatment 6 months after surgery. We have not observed any intraoperative or postoperative complications. Nonpenetrating sclerectomy allows aqueous filtration
Lung Adenocarcinoma and Malignant Uveitis Masquerade Syndrome Dear Editor: We endorse Rothova’s recommendation to use a combination of cytology and immunophenotyping as a means of identifying the primary tumor in malignant uveitis masquerade syndrome. This approach led us to a diagnosis of lung adenocarcinoma in an apparently healthy 65 year old man who had smoked for 40 years and presented with progressive vitritis in his right eye. Cytology from a diagnostic vitrectomy showed nuclear hyperchromasia and pleomorphism with mitotic figures together with cellular cohesion, vacuolated cytoplasm (black arrowheads), and occasional signet ring forms (open black arrow) supporting a diagnosis of adenocarcinoma (Figure 1). The expression of keratins (AE1:AE3 and CAM 5.2) and carcinoembryonic antigen (CEA) on immunoperoxidase staining, with the lack of staining for leukocyte common antigen (CD45), vimentin and S-100 protein were compatible with carcinoma. The expression of cytokeratin 7 and thyroid transcription factor 1 (TTF-1), without expression of cytokeratin 20, suggested a pulmonary primary. Subsequent clinical assessment, chest Xray, sputum cytology, liver function tests, barium enema, and throat endoscopy were negative. Computerized tomography later confirmed the presence of a lesion in the upper lobe of the right lung primary tumor with hilar lymphadenopathy (Figure 2). Aqueous sampling prior to the CT scan had reproduced the cellular findings, highlighting the value of paracentesis as a
Figure 1. Marked nuclear hyperchromasia and pleomorphism with mitotic figures, combined with cellular cohesion, vacuolated cytoplasm (black arrowheads) and occasional signet ring forms (open black arrow) support a diagnosis of adenocarcinoma. The expression of keratins (AE1: AE3 and CAM 5.2) and carcinoembryonic antigen (CEA) on immunoperoxidase staining, with the lack of staining for leukocyte common antigen (CD45), vimentin and S-100 protein confirm a carcinoma. The expression of cytokeratin 7 and thyroid transcription factor 1 (TTF-1), without expression of cytokeratin 20, is compatible with a pulmonary primary.
Figure 2. A hyper-dense lesion in the upper lobe of the right lung in association with hilar lymphadenopathy confirms the presence of a lung primary.
less invasive diagnostic option compared with a formal vitrectomy. CHETAN K. PATEL, BSC., FRCOPHTH WAI CHING LAM, MD, FRCS(C) SCOTT BOERNER, MD, FRCP(C) Toronto, Ontario, Canada Author reply Dear Editor: Dr. Patel et al demonstrate positive cytologic findings and immunperoxidase staining of aqueous and vitreous fluids in a patient with an intraocular metastasis of lung adenocarcinoma. They highlight the possibility of diagnosing patients suspected of having intraocular malignancy by means of aqueous analysis, which was also one of the conclusions of our study. In our study of 19 patients with malignant uveitis masquerade syndrome, five of eight aqueous samples examined gave positive results, so that in these five cases a more traumatic vitrectomy was not necessary. Pars plana vitrectomy is a more aggressive diagnostic procedure and is associated with a considerable number of postoperative complications. In addition, the possibility of inducing new metastases by handling the tissues is certainly greater with vitrectomy than with transcorneal collection of aqueous fluid. It should be noted, however, that no data are available on sensitivities of aqueous and vitreous cytologic and immunophenotyping examinations in ocular malignancies. In our study, five of eight (63%) aqueous samples were positive (2 of 3 with cytology and 3 of 5 with immunophenotyping), as well as 8 of 14 (57%) vitreous samples (5 of 9 with cytology and 3 of 5 with immunophenotyping). However, no definitive conclusions can be drawn from this small number of patients with various malignancies.
2151
Ophthalmology Volume 108, Number 12, December 2001 It is important to note that the negative cytologic results on aqueous do not exclude the presence of intraocular malignancy, and in such cases, one should proceed with further diagnostic examinations to ascertain the definitive diagnosis. At present, the aqueous analysis might be an acceptable initial diagnostic procedure, which might in a certain percentage of patients (in our study more than 50%) preclude a more aggressive diagnostic vitrectomy. ANIKI ROTHOVA, MD, PHD Utrecht, The Netherlands
Corneal Effects of Latanoprost and Timolol Dear Editor: In the article and discussion by Lass et al on the corneal effects of latanoprost and timolol (Ophthalmology 2001; 108:264 –71), I was struck by the certainty of the statement in their discussion that “The. . .increase in. . .cell density at one year for. . . latanoprost. . . “does not represent an actual increase in cell density. . .” (my italics). Although this would seem a reasonable interpretation based on what (little) we know about the effects of this class of drugs on various tissues and about endothelial cell physiology and reproductive ability, in fact, the best that can be inferred from their presented data is that if there is a change, it falls within the “error of measurement.” Whether latanoprost has a small effect on endothelial cell density cannot be determined from the data presented. Given the somewhat unusual effects that latanoprost has been noted to have on some tissues, it would seem prudent to keep an open mind with regard to its effects on other tissues. GEORGE F. CORRENT, MD, PHD Ft. Lauderdale, Florida
Topical Ketorolac after Cataract Surgery Dear Editor: For approximately one year I have been using ketorolac as my sole anti-inflammatory in conjunction with a fluoroquinolone after cataract surgery. Thus, I was very interested in the article by Solomon et al.1 With the introduction of phaco-chop, I had seen a reduction in postoperative inflammation and corneal edema in the average patient. Topical anesthesia has yielded less postoperative discomfort than in previous cases with peri- or retrobulbar anesthesia. I have also learned that ketorolac is used widely for pain control after orthopedic cases. Additionally, I question the use of steroids in the perioperative period when the most feared complication is infection. All of these factors led me to ketorolac after phacoemulsification. Overall, I have been very pleased by the results. Postoperative discomfort is minimal and patients tolerate the burning well. Modest corneal edema clears rapidly. Anterior chamber cell and flare clear more slowly so it is important that inflammation is low from the start. While I have no hard data, CME seems less common, and when it does occur it responds quickly to the addition of topical steroids. There are certain cases in which I will always use prednisolone together with ketorolac: previous history of CME, previous history of iritis, severe corneal edema/dystrophy, severe cell and flare, and capsular rupture with/without vitrectomy. I will also start steroids if cell and flare are still significant at three to four weeks after the surgery. I feel that ketorolac is a viable alternative to steroids in uncomplicated phacoemulsification. I have no interest in nor am I employed by Allergan pharmaceuticals.
Author reply Dear Editor: Dr. Corrent has raised concern about how definitive our statement that the “. . .marginal increase in average cell density at one year for the latanoprost group and the FC group does not represent an actual increase in the cell density of these subjects. . .” I believe we both are in agreement that this slight increase in these two groups relates solely to an error of measurement in the cell density determination technique, as stated in the article. We believe that this is not due to any stimulatory effect of latanoprost or its combination on endothelial replication, given the limited potential for such replication in the normal or injured cornea. I agree with Dr. Corrent, however, that we cannot absolutely conclude this from our study, and I would therefore modify our statement from “does not” to “most likely does not.” At the same time, it is important to emphasize that there was no significant difference in the mean change in central endothelial cell density between the three groups, including the timolol group, at 1 year, and that the change was “comparable with the rate of change of approximately 0.6% cell loss annually. . .in a normally aging population.26” JONATHAN H. LASS, MD Cleveland, Ohio
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CHARLES J. KAISER, MD Miami, Florida REFERENCE 1. Solomon KD, Cheetham JK, DeGryse R, et al. Topical ketorolac tromethamine 0.5% ophthalmic solution in ocular inflammation after cataract surgery. Ophthalmology 2001;108:331–7.
Nonpenetrating Deep Sclerectomy for SturgeWeber Syndrome Dear Editor: Budenz et al1 have recently reported their results with the two-stage Baervedlt implant combined with prophylactic sclerostomies in children with late-onset glaucoma in Sturge-Weber syndrome (SWS). This surgical approach minimized the risk for choroidal effusions and hemorrhages; however, it did not eliminate it, and choroidal effusions occurred in 2 of 10 eyes (20%). We have performed a nonpenetrating deep sclerectomy with a reticulated hyaluronic acid implant in a 17-year-old patient with SWS and secondary glaucoma in the right eye. Preoperative intraocular pressure (IOP) was 30 mmHg with medical therapy, and postoperative IOP was 15 mmHg without treatment 6 months after surgery. We have not observed any intraoperative or postoperative complications. Nonpenetrating sclerectomy allows aqueous filtration