Klinische Wochenschrift
Klin Wochenschr (1990) 68:1027-1031
9 Springer-Verlag 1990
Case Reports Systemic Malignant Lymphoma Presenting As Bilateral Exudative Retinal Detachment B.A. Kormann 1, H. Holzgreve 1, P.G. Wolff-Kormann 2, and K.G. Riedel 2 i Medizinische Poliklinik der Universit/it Miinchen (Prof. Dr. N. Z611ner) 2 Augenklinik der Universit/it Mfinchen (Prof. Dr. O.-E. Lund)
Summary. A 52-year-old male patient presented with a sudden painful loss of vision in both eyes. Ophthahnological examination revealed bilateral uveitis and marked bilateral nonrhegmatogenous retinal detachment near the optic disk. Systemic workup demonstrated IgM paraproteinemia. Abdominal ultrasound and computed tomographic studies revealed enlarged adrenal glands and irregular masses in the right hepatic lobe. Immune electrophoresis and multiple biopsy specimens established the diagnosis of systemic polymorphous immunocytoma. Polychemotherapy of this B-cell-derived type of non-Hodgkin's lymphoma led to a rapid remission and fast reduction of serous retinal detachment. We believe this is the first case of bilateral exudative retinal detachment as the initial ocular manifestation of systemic malignant B-cell lymphoma.
indicated a 3:1 female-to-male ratio [16]. Frequently the posterior segment is affected, demonstrating choroiditis [4, 8, 11] or infiltrative retinopathy [6, 25]. Retinal hemorrhages have also been reported [20, 23]. Nonrhegmatogenous retinal detachment is rare and usually appears as a late manifestation [10]. Unilateral exudative retinal detachment has been described in primary intraocular reticulum cell sarcoma [11, 23], in primary intraocular B-cell lymphoma [1, 3], and in primary cerebral reticulum cell sarcoma-microglioma [10]. One case of bilateral exudative retinal detachment and conjunctival hemorrhages was reported by Pau and Schneider in 1980 [13] in systemic T-cell lymphoma. In this communication we describe a case of systemic malignant B-cell lymphoma initially presenting as a bilateral exudative retinal detachment.
Key words: Retinal d e t a c h m e n t - Uveitis - Malig-
Case Report
nant lymphoma - Immunocytoma
Intraocular involvement of systemic malignant lymphoma is rare. Only 12 (17.6%) of the 68 cases of intraocular lymphoma cited in the world literature [3] were associated with systemic lymphoma. The most common ocular presentation of systemic malignant lymphoma is bilateral chronic uveitis unresponsive to topical or systemic corticosteroid treatment [17]. It is often referred to as masquerade syndrome and usually occurs in middle-aged or elderly patients. Current data so far suggest no sexual predeliction [18], whereas former findings Abbreviations." Ig A = Immunglobulin A; Ig M : lmmunglobulin M; q d = e v e r y day; O D = r i g h t eye; O S = l e f t eye; C T = computerized tomography
A 52-year-old man was admitted to the University of Munich Eye Hospital on May 29, 1988 because of bilateral loss of vision that was unresponsive to treatment. He had been healthy until August 1987, when he began to suffer from weakness, night sweats, and weight loss. An elevated erythrocyte sedimentation rate, leukocytosis, and paraproteinemia were diagnosed 5 months before admission. Two weeks before entry he experienced progressive blurring of vision in the right eye that was followed by right retroorbital pain and a significant decrease of central vision. Orally corticosteroid therapy administered because of suspected uveitis did not improve vision in the right eye. Left retroorbital pain combined with a sudden loss of vision in the left eye occurred nine days later. Ophthalmological examination showed a visual acuity in the right eye of 10/200 (metric 1/20) and
1028
B.A. Kormann et al. : Systemic Malignant Lymphoma
Fig. 2. Right eye: Pretreatment photograph of peripheral fundus with multiple white-yellow placoid subretinal lesions
Fig. l a, b. Pretreatment photographs of the central fundus showing bilateral exudative retinal detachment near the optic disc (arrows). a right eye; b left eye
20/160 (metric 0.3) in the left eye non-correctable. Ocular motility and pupillary reactions were normal. The intraocular pressure was 14 mm Hg bilaterally. Slit lamp examination revealed bilateral conjunctival injection and slight ciliary reaction in the right eye. There was no evidence of keratitic precipitates. Anterior chambers were deep with inflammatory cells in the right chamber and trace cells in the left. The iris was normal, the lens clear bilaterally. The vitreous in both eyes contained in-
flammatory cells. Indirect ophthalmoscopy revealed central retinal detachment in the right eye extending to the 5-o'clock and 7-o'clock positions with subretinal fluid (Fig. 1 a). The left eye also demonstrated central retinal detachment with shifting fluid (Fig. 1 b). In addition to the findings of bilateral nonrhegmatogenous retinal detachment, there were irregular yellowish-white subretinal placoid lesions (Fig. 2). The patient received prednisone 60 mg qd together with dilating and steroid drops. His symptoms deteriorated quickly. A follow-up examination three days later revealed extended exudative retinal detachment and decreased visual acuity to hand motion OD and 20/200 (metric 0.1) OS. He was transferred to the Department of Internal Medicine where he underwent extensive examination to evaluate a possible underlying systemic disease. Physical examination showed no hepatosplenomegaly or lymphadenopathy. Laboratory data showed the following pathological values: hemoglobin 12.8 g/dl; hematocrit 37.7% ; and white cell count 21900 with 81 per cent segmented neutrophils, 1 per cent basophils, 14 per cent lymphocytes, and 4 per cent monocytes. The platelet count was 288000, and the erythrocyte sedimentation was 84 m m per hour. Bilirubin was 1.6 mg/dl and uric acid, 28 mg/dl. Iron measured 16 ~tg/dl; the iron binding capacity was 201 gg/dl. Serum aspartate aminotransferase was 27 U, serum alanine
B.A. Kormann et al. : Systemic Malignant Lymphoma
1029
Fig. 3. Abdominal ultrasound photograph demonstrating enlarged adrenal gland and heterogenous area of decreased echographic texture in the right hepatic lobe (arrows)
aminotransferase, 67 U, lactic dehydrogenase (LDH), 523 U, and alkaline phosphatase, 216 U per liter. Serum immunoelectrophoresis showed an abnormal IgM precipitin arc. Quantitative studies disclosed that lgM was 11.65 g/1. There was no sign of paraproteinemia. Immune electrophoresis revealed oligoclonal proteinuria of the kappa type. An X-ray film and computed tomographic scan of the chest and the brain performed after the infusion of contrast material were normal. An ultrasound study of the abdomen demonstrated heterogeneous areas of decreased echographic texture in the liver and the adrenal glands (Fig. 3). A computed tomographic scan of the abdomen revealed no evidence of lymphadenopathy, but the adrenal glands appeared enlarged, and rounded masses with irregular borders without enhancement of contrast material were noted in the right hepatic lobe. Under CT-scan guidance a needle aspiration biopsy of the masses was performed. Histological examination of the aspirated specimens and immunological investigations (negative reaction of tumor cells with the T-cell-associated antibody UCHL I and positive reaction with the B-cell-associated antibody L 26) established the diagnosis of malignant non-Hodgkin's lymphoma (polymorphous immunocytoma). Radionuclide bone scan using technetium 99 was negative. Bone marrow biopsy disclosed atypical megakaryocytes and abnormal lymphoid cells thought to be consistent with B-cell non-Hodgkin's lymphoma. A combination chemotherapy using cyclophosphamide (800 mg/dl), vincristirie (2 rag/d l), prednisone (80mg/dl-10), bleomycin (15mg/ d14), adriamycin (80 mg/d]), and procarbazine (200 mg/dl-10) - acronym COPBLAM - was started on June 10, 1988.
Fig. 4a, b. Photographs of central fundus during the first cycle of polychemotherapy showing marked reduction of bilateral exudative retinal detachment (arrows). a right eye; b left eye
Follow-up examinations disclosed signs of remission after two weeks. Ultrasound and computed tomographic scan of the abdomen showed no more evidence of hepatic masses. Adrenal glands also appeared normal. Ophthalmological workup on June 27, 1988 demonstrated bilateral increase of vision. In the right eye visual acuity had improved to 20/125 (metric 0.4) and in the left eye, to 20/50 (metric 0.7). There was still sparse exudate in the anterior chambers and the vitreous
1030
of both eyes; however, exudative retinal detachment had flattened bilaterally (Figs. 4a and 4b). After the initial induction cycle four further cycles of COPBLAM chemotherapy were administered. Unfortunately, the patient expired on October 24, 1988 as a result of respiratory failure due to spontaneous pneumothorax.
Discussion
A 52-year-old patient presented with sudden bilateral loss of vision due to nonreghmatogenous retinal detachment in both eyes. Bilateral exudative retinal detachment may occur with choroidal metastatic or retinal tumors (angioma, retinoblastoma; choroidal melanoma [5]), inflammatory or parasitic disorders such as Harada's disease or toxocariasis, and malignant hypertension [12]. None of these possible diagnoses could be confirmed. The differential diagnosis of sudden bilateral loss of vision unresponsive to corticosteroid treatment should also include ocular involvement by chronic myelogenous or chronic myelomonocytic leukemia. Current estimates of prevalence rates for ocular manifestations of leukemia range from 9-42% [19]. In our patient leukocytosis was due to corticisteroid treatment initially administered by the ophthalmologist. To assess the possibility of malignant lymphoma in terms of tumor masses, extensive investigations were undertaken, including an abdominal ultrasound study and a computerized scan of the abdomen. The diagnosis of systemic polymorphous immunocytoma was finally established by histological and immunological evaluation of biopsy specimens taken from adrenal gland and hepatic masses as well as by bone marrow biopsy. Anemia and thrombocytopenia pointed to bone marrow infiltration by B-cell lymphoma. Pathological liver enzymes reflected liver involvement in pleomorphous immunocytoma and the massive increase of uric acid indicated an elevated turnover of tumor cells. The differential diagnosis of multiple myeloma was ruled out by clinical, radiological, and laboratory features. Extralymphatic organ involvement may occur in immunocytoma, a malignant tumor of lymphoid tissue affecting the B lymphocytes [9, 22]. Our patient was among the 95 per cent of patients who suffer from advanced disease, stage IV according to the Ann Arbor Classification at the time of staging evaluation [21, 24]. Pathological studies of eyes with clinically suspicious evidence of intraocular lymphoma have revealed the destruction of normal retinal architec-
B.A. Kormann et al. : Systemic Malignant Lymphoma
ture as a result of massive infiltration by neoplastic cells. Clusters of tumor cells have been detected between Bruch's membrane and the retinal pigment epithelium and within the subretinal space explaining nonrhegmatogenous retinal detachment in intraocular lymphoma [1, 23]. In the past, ocular involvement by lymphoma has usually been diagnosed after enucleation of a blind, painful eye or at postmortem examination. The development of a modern fine-needle vitreous biopsy technique in the past decade provides clues to the diagnosis of intraocular lymphoma. It allows visualization of the vitreous cavity during the procedure by the use of an intraocular fiberoptic light source and an operating microscope like this minimizing the danger to the retina. Immunologic and cytochemical characterization of vitrectomy material such as immunoperoxidase staining for the presence of cell surface immunoglobulins [7] provides the exact classification of intraocular lymphomas. Usually primary intraocular or cerebral malignant lymphoma has been morphologically classified as histiocytic lymphoma or reticulum cell lymphoma. Since immunology has elucidated the multifaceted disease spectrum of lymphomas, this model should be revised. Cell surface marker and in-vitro lymphocyte function studies on histiocytic lymphomas have consistently demonstrated them to be lymphoid and only in 5% of truly histiocytic origin [2, 14, 15]. These findings suggest the susceptibility of B-cell-derived intraocular lymphomas to chemotherapy [7], providing new approaches to the treatment of intraocular lymphoma. In our patient sudden bilateral loss of vision turned out to be a manifestation of extraocular malignant B-cell lymphoma, so this malignancy should be included in the differential diagnosis of bilateral exudative retinal detachment. Rapid remission of polymorphous immunocytoma and fast reduction of bilateral nonreghmatogenous retinal detachment after polychemotherapy emphasize the importance of prompt recognition of malignant Bcell lymphoma. Systemic malignant lymphoma is usually diagnosed before eye involvement occurs. We believe this is the first case of systemic malignant B-cell lymphoma (polymorphous immunocytoma) initially presenting with bilateral exudative retinal detachment. References 1. Bechcinska B, Sporny S, Witczak E (1986) Malignes Lymphom des Auges. Zentralbl Allg Pathol 132:307 311
B.A. Kormann et al. : Systemic Malignant Lymphoma 2. Born-van Noorloos AA, Splinter TAW, Heerde PV et al. (1973) Surface markers and functional properties of nonHodgkin's lymphoma cells in relation to histology. Cancer 42:1804-1817 3. Corriveau C, Easterbrook M, Payne D (1986) Lymphoma simulating uveitis (masquerade syndrome). Can J Ophthaltool 21 : 144-149 4. Duker HS, Shields JA, Ross M (1987) Intraocular large cell lymphoma presenting as massive thickening of the uveal tract. Retina 7 : 41-45 5. Fraunfelder FT, Roy FH (1990) Current ocular therapy, 3rd edn. Saunders, Philadelphia, p 675 6. Jack CR, O'Neill BP, Banks PM, Reese DF (1988) Central nervous system lymphoma: histologic types and CT appearance. Radiology 167: 211-215 7. Kaplan JH, Meredith TA, Aaberg TM, Keller RH (1980) Reclassification of intraocular reticulum cell sarcoma (histiocytic lymphoma). Arch Ophthalmol 98:707-710 8. Klingele TG, Hogan MJ (1975) Ocular reticnlum cell sarcoma. Am J Ophthalmol 79:39-47 9. Lennert K (1978) Malignant lymphomas other than Hodgkin's disease. In: Uehlinger E (ed) Handbuch der speziellen pathologischen Anatomie und Histologie. Bd I/3B, Springer, Berlin Heidelberg New York 10. Michelson JB, Michelson PE, Bordin GM, Chisari FV (1981) Ocular reticulum cell sarcoma. Arch Ophthalmol 99:1409-1411 11. Parver LM, Font RL (1979) Malignant lymphoma of the retina and the brain. Arch Ophthalmol 97:1505-1507 12. Pau H (1986) Differentialdiagnose der Augenkrankheiten. Thieme, Stuttgart, S 359-360 13. Pau H, Schneider W (1980) Vorfibergehende Netzhautabl6sung und Hyposphagma bei einem Patienten mit NonHodgkin-Lymphom vom T-Zell-Typ. Ophthalmologica 181 : 160-164 14. Piessens WF, Schur PH, Moloney WC et al. (1973) Lymphocytes' surface immunoglobulins: distribution and frequency in lymphoproliferative diseases. N Engl J Med 288 : 176-180 15. Pinkus GS, Said JW (1979) Characterization of non-Hodgkin's lymphomas using multiple cell markers: immunological, morphological and cytochemical studies of 72 cases. Am J Pathol 94:349-376
1031 16. Qualman SJ, Mendelsohn G, Mann RB, Green WR (1982) Intraocular lymphomas. Cancer 52 : 878-886 17. Rockwood EJ, Zakov N, Bay JW (1984) Combined malignant lymphoma of the eye and the CNS (reticulum cell sarcoma). J Neurosurg 61 : 369-374 18. Saga T, Ohno S, Matsuda H, Ogasawara M, Kikuchi K (1984) Ocular involvement by a peripheral T-cell lymphoma. Arch Ophthahnol 102:399-402 19. Schachat AP, Markowitz JA, Guyer DR, Burke PJ, Karp JE, Graham ML (1989) Ophthalmic manifestations of leukemia. Arch Ophthalmol 107:697-700 20. Sullivan SF, Dallow RL (1977) Intraocular reticulum cell sarcoma: its dramatic response to systemic chemotherapy and its angiogenic potential. Ann Ophthalmol 9:401-406 21. Theml H, Bartels H, Brittinger G e t al. (1983) Klinik und Prognose der Non-Hodgkin-Lymphome vom niedrigen Malignit/itsgrad: Ergebnisse einer multizentrischen prospektiyen Studie an 1127 F/illen. Verh Dtsch Ges Inn Med 89 : 352-370 22. Theml H (1986) Maligne Non-Hodgkin-Lymphome. In: Begemann H, Rastetter J (eds) Klinische H/imatologie, 3rd edn. Thieme, Stuttgart, p 678-779 23. Vogel MH, Font RL, Zimmerman LE, Levine RA (1968) Reticulum cell sarcoma of the retina and uvea. Am J Ophthalmol 66 : 205-215 24. Wedelin C, Bj6rkholm M, Biberfeld P, Holm G, Johansson B, Mellstedt H (1984) Prognostic factors in Hodgkin's disease with special reference to age. Cancer 53:1202-1209 25. Yen MY, Liu JH (1985) Malignant lymphoma involving the optic nerve head and the retina. Arch Ophthalmol 17 : 697-700
Received May 16, 1990 Returned for revision: July 16, 1990 Accepted: August 3, 1990
Dr. B.A. Kormann Medizinische Poliklinik der Universit/it Mfinchen Pettenkoferstr. 8a D-8000 Mfinchen 2
Klin Wochenschr (1990) 68:1027-1031
9 Springer-Verlag 1990
Case Reports Systemic Malignant Lymphoma Presenting As Bilateral Exudative Retinal Detachment B.A. Kormann 1, H. Holzgreve 1, P.G. Wolff-Kormann 2, and K.G. Riedel 2 i Medizinische Poliklinik der Universit/it Miinchen (Prof. Dr. N. Z611ner) 2 Augenklinik der Universit/it Mfinchen (Prof. Dr. O.-E. Lund)
Summary. A 52-year-old male patient presented with a sudden painful loss of vision in both eyes. Ophthahnological examination revealed bilateral uveitis and marked bilateral nonrhegmatogenous retinal detachment near the optic disk. Systemic workup demonstrated IgM paraproteinemia. Abdominal ultrasound and computed tomographic studies revealed enlarged adrenal glands and irregular masses in the right hepatic lobe. Immune electrophoresis and multiple biopsy specimens established the diagnosis of systemic polymorphous immunocytoma. Polychemotherapy of this B-cell-derived type of non-Hodgkin's lymphoma led to a rapid remission and fast reduction of serous retinal detachment. We believe this is the first case of bilateral exudative retinal detachment as the initial ocular manifestation of systemic malignant B-cell lymphoma.
indicated a 3:1 female-to-male ratio [16]. Frequently the posterior segment is affected, demonstrating choroiditis [4, 8, 11] or infiltrative retinopathy [6, 25]. Retinal hemorrhages have also been reported [20, 23]. Nonrhegmatogenous retinal detachment is rare and usually appears as a late manifestation [10]. Unilateral exudative retinal detachment has been described in primary intraocular reticulum cell sarcoma [11, 23], in primary intraocular B-cell lymphoma [1, 3], and in primary cerebral reticulum cell sarcoma-microglioma [10]. One case of bilateral exudative retinal detachment and conjunctival hemorrhages was reported by Pau and Schneider in 1980 [13] in systemic T-cell lymphoma. In this communication we describe a case of systemic malignant B-cell lymphoma initially presenting as a bilateral exudative retinal detachment.
Key words: Retinal d e t a c h m e n t - Uveitis - Malig-
Case Report
nant lymphoma - Immunocytoma
Intraocular involvement of systemic malignant lymphoma is rare. Only 12 (17.6%) of the 68 cases of intraocular lymphoma cited in the world literature [3] were associated with systemic lymphoma. The most common ocular presentation of systemic malignant lymphoma is bilateral chronic uveitis unresponsive to topical or systemic corticosteroid treatment [17]. It is often referred to as masquerade syndrome and usually occurs in middle-aged or elderly patients. Current data so far suggest no sexual predeliction [18], whereas former findings Abbreviations." Ig A = Immunglobulin A; Ig M : lmmunglobulin M; q d = e v e r y day; O D = r i g h t eye; O S = l e f t eye; C T = computerized tomography
A 52-year-old man was admitted to the University of Munich Eye Hospital on May 29, 1988 because of bilateral loss of vision that was unresponsive to treatment. He had been healthy until August 1987, when he began to suffer from weakness, night sweats, and weight loss. An elevated erythrocyte sedimentation rate, leukocytosis, and paraproteinemia were diagnosed 5 months before admission. Two weeks before entry he experienced progressive blurring of vision in the right eye that was followed by right retroorbital pain and a significant decrease of central vision. Orally corticosteroid therapy administered because of suspected uveitis did not improve vision in the right eye. Left retroorbital pain combined with a sudden loss of vision in the left eye occurred nine days later. Ophthalmological examination showed a visual acuity in the right eye of 10/200 (metric 1/20) and
1028
B.A. Kormann et al. : Systemic Malignant Lymphoma
Fig. 2. Right eye: Pretreatment photograph of peripheral fundus with multiple white-yellow placoid subretinal lesions
Fig. l a, b. Pretreatment photographs of the central fundus showing bilateral exudative retinal detachment near the optic disc (arrows). a right eye; b left eye
20/160 (metric 0.3) in the left eye non-correctable. Ocular motility and pupillary reactions were normal. The intraocular pressure was 14 mm Hg bilaterally. Slit lamp examination revealed bilateral conjunctival injection and slight ciliary reaction in the right eye. There was no evidence of keratitic precipitates. Anterior chambers were deep with inflammatory cells in the right chamber and trace cells in the left. The iris was normal, the lens clear bilaterally. The vitreous in both eyes contained in-
flammatory cells. Indirect ophthalmoscopy revealed central retinal detachment in the right eye extending to the 5-o'clock and 7-o'clock positions with subretinal fluid (Fig. 1 a). The left eye also demonstrated central retinal detachment with shifting fluid (Fig. 1 b). In addition to the findings of bilateral nonrhegmatogenous retinal detachment, there were irregular yellowish-white subretinal placoid lesions (Fig. 2). The patient received prednisone 60 mg qd together with dilating and steroid drops. His symptoms deteriorated quickly. A follow-up examination three days later revealed extended exudative retinal detachment and decreased visual acuity to hand motion OD and 20/200 (metric 0.1) OS. He was transferred to the Department of Internal Medicine where he underwent extensive examination to evaluate a possible underlying systemic disease. Physical examination showed no hepatosplenomegaly or lymphadenopathy. Laboratory data showed the following pathological values: hemoglobin 12.8 g/dl; hematocrit 37.7% ; and white cell count 21900 with 81 per cent segmented neutrophils, 1 per cent basophils, 14 per cent lymphocytes, and 4 per cent monocytes. The platelet count was 288000, and the erythrocyte sedimentation was 84 m m per hour. Bilirubin was 1.6 mg/dl and uric acid, 28 mg/dl. Iron measured 16 ~tg/dl; the iron binding capacity was 201 gg/dl. Serum aspartate aminotransferase was 27 U, serum alanine
B.A. Kormann et al. : Systemic Malignant Lymphoma
1029
Fig. 3. Abdominal ultrasound photograph demonstrating enlarged adrenal gland and heterogenous area of decreased echographic texture in the right hepatic lobe (arrows)
aminotransferase, 67 U, lactic dehydrogenase (LDH), 523 U, and alkaline phosphatase, 216 U per liter. Serum immunoelectrophoresis showed an abnormal IgM precipitin arc. Quantitative studies disclosed that lgM was 11.65 g/1. There was no sign of paraproteinemia. Immune electrophoresis revealed oligoclonal proteinuria of the kappa type. An X-ray film and computed tomographic scan of the chest and the brain performed after the infusion of contrast material were normal. An ultrasound study of the abdomen demonstrated heterogeneous areas of decreased echographic texture in the liver and the adrenal glands (Fig. 3). A computed tomographic scan of the abdomen revealed no evidence of lymphadenopathy, but the adrenal glands appeared enlarged, and rounded masses with irregular borders without enhancement of contrast material were noted in the right hepatic lobe. Under CT-scan guidance a needle aspiration biopsy of the masses was performed. Histological examination of the aspirated specimens and immunological investigations (negative reaction of tumor cells with the T-cell-associated antibody UCHL I and positive reaction with the B-cell-associated antibody L 26) established the diagnosis of malignant non-Hodgkin's lymphoma (polymorphous immunocytoma). Radionuclide bone scan using technetium 99 was negative. Bone marrow biopsy disclosed atypical megakaryocytes and abnormal lymphoid cells thought to be consistent with B-cell non-Hodgkin's lymphoma. A combination chemotherapy using cyclophosphamide (800 mg/dl), vincristirie (2 rag/d l), prednisone (80mg/dl-10), bleomycin (15mg/ d14), adriamycin (80 mg/d]), and procarbazine (200 mg/dl-10) - acronym COPBLAM - was started on June 10, 1988.
Fig. 4a, b. Photographs of central fundus during the first cycle of polychemotherapy showing marked reduction of bilateral exudative retinal detachment (arrows). a right eye; b left eye
Follow-up examinations disclosed signs of remission after two weeks. Ultrasound and computed tomographic scan of the abdomen showed no more evidence of hepatic masses. Adrenal glands also appeared normal. Ophthalmological workup on June 27, 1988 demonstrated bilateral increase of vision. In the right eye visual acuity had improved to 20/125 (metric 0.4) and in the left eye, to 20/50 (metric 0.7). There was still sparse exudate in the anterior chambers and the vitreous
1030
of both eyes; however, exudative retinal detachment had flattened bilaterally (Figs. 4a and 4b). After the initial induction cycle four further cycles of COPBLAM chemotherapy were administered. Unfortunately, the patient expired on October 24, 1988 as a result of respiratory failure due to spontaneous pneumothorax.
Discussion
A 52-year-old patient presented with sudden bilateral loss of vision due to nonreghmatogenous retinal detachment in both eyes. Bilateral exudative retinal detachment may occur with choroidal metastatic or retinal tumors (angioma, retinoblastoma; choroidal melanoma [5]), inflammatory or parasitic disorders such as Harada's disease or toxocariasis, and malignant hypertension [12]. None of these possible diagnoses could be confirmed. The differential diagnosis of sudden bilateral loss of vision unresponsive to corticosteroid treatment should also include ocular involvement by chronic myelogenous or chronic myelomonocytic leukemia. Current estimates of prevalence rates for ocular manifestations of leukemia range from 9-42% [19]. In our patient leukocytosis was due to corticisteroid treatment initially administered by the ophthalmologist. To assess the possibility of malignant lymphoma in terms of tumor masses, extensive investigations were undertaken, including an abdominal ultrasound study and a computerized scan of the abdomen. The diagnosis of systemic polymorphous immunocytoma was finally established by histological and immunological evaluation of biopsy specimens taken from adrenal gland and hepatic masses as well as by bone marrow biopsy. Anemia and thrombocytopenia pointed to bone marrow infiltration by B-cell lymphoma. Pathological liver enzymes reflected liver involvement in pleomorphous immunocytoma and the massive increase of uric acid indicated an elevated turnover of tumor cells. The differential diagnosis of multiple myeloma was ruled out by clinical, radiological, and laboratory features. Extralymphatic organ involvement may occur in immunocytoma, a malignant tumor of lymphoid tissue affecting the B lymphocytes [9, 22]. Our patient was among the 95 per cent of patients who suffer from advanced disease, stage IV according to the Ann Arbor Classification at the time of staging evaluation [21, 24]. Pathological studies of eyes with clinically suspicious evidence of intraocular lymphoma have revealed the destruction of normal retinal architec-
B.A. Kormann et al. : Systemic Malignant Lymphoma
ture as a result of massive infiltration by neoplastic cells. Clusters of tumor cells have been detected between Bruch's membrane and the retinal pigment epithelium and within the subretinal space explaining nonrhegmatogenous retinal detachment in intraocular lymphoma [1, 23]. In the past, ocular involvement by lymphoma has usually been diagnosed after enucleation of a blind, painful eye or at postmortem examination. The development of a modern fine-needle vitreous biopsy technique in the past decade provides clues to the diagnosis of intraocular lymphoma. It allows visualization of the vitreous cavity during the procedure by the use of an intraocular fiberoptic light source and an operating microscope like this minimizing the danger to the retina. Immunologic and cytochemical characterization of vitrectomy material such as immunoperoxidase staining for the presence of cell surface immunoglobulins [7] provides the exact classification of intraocular lymphomas. Usually primary intraocular or cerebral malignant lymphoma has been morphologically classified as histiocytic lymphoma or reticulum cell lymphoma. Since immunology has elucidated the multifaceted disease spectrum of lymphomas, this model should be revised. Cell surface marker and in-vitro lymphocyte function studies on histiocytic lymphomas have consistently demonstrated them to be lymphoid and only in 5% of truly histiocytic origin [2, 14, 15]. These findings suggest the susceptibility of B-cell-derived intraocular lymphomas to chemotherapy [7], providing new approaches to the treatment of intraocular lymphoma. In our patient sudden bilateral loss of vision turned out to be a manifestation of extraocular malignant B-cell lymphoma, so this malignancy should be included in the differential diagnosis of bilateral exudative retinal detachment. Rapid remission of polymorphous immunocytoma and fast reduction of bilateral nonreghmatogenous retinal detachment after polychemotherapy emphasize the importance of prompt recognition of malignant Bcell lymphoma. Systemic malignant lymphoma is usually diagnosed before eye involvement occurs. We believe this is the first case of systemic malignant B-cell lymphoma (polymorphous immunocytoma) initially presenting with bilateral exudative retinal detachment. References 1. Bechcinska B, Sporny S, Witczak E (1986) Malignes Lymphom des Auges. Zentralbl Allg Pathol 132:307 311
B.A. Kormann et al. : Systemic Malignant Lymphoma 2. Born-van Noorloos AA, Splinter TAW, Heerde PV et al. (1973) Surface markers and functional properties of nonHodgkin's lymphoma cells in relation to histology. Cancer 42:1804-1817 3. Corriveau C, Easterbrook M, Payne D (1986) Lymphoma simulating uveitis (masquerade syndrome). Can J Ophthaltool 21 : 144-149 4. Duker HS, Shields JA, Ross M (1987) Intraocular large cell lymphoma presenting as massive thickening of the uveal tract. Retina 7 : 41-45 5. Fraunfelder FT, Roy FH (1990) Current ocular therapy, 3rd edn. Saunders, Philadelphia, p 675 6. Jack CR, O'Neill BP, Banks PM, Reese DF (1988) Central nervous system lymphoma: histologic types and CT appearance. Radiology 167: 211-215 7. Kaplan JH, Meredith TA, Aaberg TM, Keller RH (1980) Reclassification of intraocular reticulum cell sarcoma (histiocytic lymphoma). Arch Ophthalmol 98:707-710 8. Klingele TG, Hogan MJ (1975) Ocular reticnlum cell sarcoma. Am J Ophthalmol 79:39-47 9. Lennert K (1978) Malignant lymphomas other than Hodgkin's disease. In: Uehlinger E (ed) Handbuch der speziellen pathologischen Anatomie und Histologie. Bd I/3B, Springer, Berlin Heidelberg New York 10. Michelson JB, Michelson PE, Bordin GM, Chisari FV (1981) Ocular reticulum cell sarcoma. Arch Ophthalmol 99:1409-1411 11. Parver LM, Font RL (1979) Malignant lymphoma of the retina and the brain. Arch Ophthalmol 97:1505-1507 12. Pau H (1986) Differentialdiagnose der Augenkrankheiten. Thieme, Stuttgart, S 359-360 13. Pau H, Schneider W (1980) Vorfibergehende Netzhautabl6sung und Hyposphagma bei einem Patienten mit NonHodgkin-Lymphom vom T-Zell-Typ. Ophthalmologica 181 : 160-164 14. Piessens WF, Schur PH, Moloney WC et al. (1973) Lymphocytes' surface immunoglobulins: distribution and frequency in lymphoproliferative diseases. N Engl J Med 288 : 176-180 15. Pinkus GS, Said JW (1979) Characterization of non-Hodgkin's lymphomas using multiple cell markers: immunological, morphological and cytochemical studies of 72 cases. Am J Pathol 94:349-376
1031 16. Qualman SJ, Mendelsohn G, Mann RB, Green WR (1982) Intraocular lymphomas. Cancer 52 : 878-886 17. Rockwood EJ, Zakov N, Bay JW (1984) Combined malignant lymphoma of the eye and the CNS (reticulum cell sarcoma). J Neurosurg 61 : 369-374 18. Saga T, Ohno S, Matsuda H, Ogasawara M, Kikuchi K (1984) Ocular involvement by a peripheral T-cell lymphoma. Arch Ophthahnol 102:399-402 19. Schachat AP, Markowitz JA, Guyer DR, Burke PJ, Karp JE, Graham ML (1989) Ophthalmic manifestations of leukemia. Arch Ophthalmol 107:697-700 20. Sullivan SF, Dallow RL (1977) Intraocular reticulum cell sarcoma: its dramatic response to systemic chemotherapy and its angiogenic potential. Ann Ophthalmol 9:401-406 21. Theml H, Bartels H, Brittinger G e t al. (1983) Klinik und Prognose der Non-Hodgkin-Lymphome vom niedrigen Malignit/itsgrad: Ergebnisse einer multizentrischen prospektiyen Studie an 1127 F/illen. Verh Dtsch Ges Inn Med 89 : 352-370 22. Theml H (1986) Maligne Non-Hodgkin-Lymphome. In: Begemann H, Rastetter J (eds) Klinische H/imatologie, 3rd edn. Thieme, Stuttgart, p 678-779 23. Vogel MH, Font RL, Zimmerman LE, Levine RA (1968) Reticulum cell sarcoma of the retina and uvea. Am J Ophthalmol 66 : 205-215 24. Wedelin C, Bj6rkholm M, Biberfeld P, Holm G, Johansson B, Mellstedt H (1984) Prognostic factors in Hodgkin's disease with special reference to age. Cancer 53:1202-1209 25. Yen MY, Liu JH (1985) Malignant lymphoma involving the optic nerve head and the retina. Arch Ophthalmol 17 : 697-700
Received May 16, 1990 Returned for revision: July 16, 1990 Accepted: August 3, 1990
Dr. B.A. Kormann Medizinische Poliklinik der Universit/it Mfinchen Pettenkoferstr. 8a D-8000 Mfinchen 2
![[Bilateral exudative retinal detachment as presenting sign of preeclampsia].](/assets/img/hold.png)
