OCR Text |
Show lou mal of Clinical Neuro- ophthalmology 10( 4)' 248- 254, 1990. Hodgkin's Disease at the Optic Chiasm R. M. McFadzean, F. R. C. S. Ed., G. G. McIlwaine, F. R. c. S.( Glas.), and D. McLellan, M. R. C. Path. © 1990 Raven PreS' . cw York In a case of visual loss due to infiltration of the optic chiasm by Hodgkin's lymphoma in a 44- year- old man the diagnosis was supported by histology of the optic chiasm, an axillary lymph node, and bone marrow at presentation. This appears to be only the third histologically proven reported case of Hodgkin's disease in this location, and the first diagnosed during life. Key Words: Hodgkin's lymphoma- Optic chiasm. From the Departments of Neuro- ophthalmology and Neuropathology ( D. McL.), Institute of Neurological Sciences, Southern General Hospital. Glasgow, Scotland. Address correspondence and reprint requests to Dr. R. M. McFadzean, Department of Neuro- ophthalmology, Institute of Neurological Sciences, Slluthern Cem'ral Hospital, Glasgow C53 4TF, SClltbnd 248 Hodgkin's disease is characterized by " a gradual progressive enlargement of the lymphatic glands beginning usually in the cervical region and spreading throughout lymphoid tissue of the body, forming nodular growths in the internal organs, resulting in anaemia and usually a fatal cachexia" ( 1). The first recorded intracranial case was in a 6- year- old girl ( 2). Subsequent large studies have indicated that neurological involvement occurs in 13 to 15% of patients ( 3,4), but a more recent review of 2,185 patients ( 5) revealed only 0.5% with neurological complications. This latter prevalence may be a consequence of earlier diagnosis and treatment, as most cases of neurological involvement are secondary to metastatic spread via meningeal vessels or by direct tumor extension ( 6- 10), and cerebral involvement usually develops late in the course of the disease. Occasionally, impaired neurological function may be the first and only presenting feature prior to the development of any other evidence of Hodgkin's disease ( 1114), but primary intracranial lesions have also been described ( 6,11,12,15- 17). Visual loss is an infrequent complication, due to lesions of the optic nerves and chiasm ( 18- 20) or the postchiasmal visual pathways ( 21). Pathologically, Hodgkin's disease is rare within the brain ( 22,23), but the characteristic histological picture is of a pleomorphic infiltrate including Reed- Sternberg cells, Reed- Sternberg variants, lymphocytes, plasma cells, histiocytes, eosinophils, and neutrophils associated with a variable degree of fibrosis and necrosis. CASE STUDY A 44- year- old man presented with progressive loss of vision and flashing lights in both eyes over a period of 2 months. He also complained of excessive thirst and passage of urine with imrotence and hair loss. Postcoital headaches had occurred during the preceding 5 years. HODGKiN'S DISEASE AT THE OPTIC CHIASM 249 Examination showed corrected visual acuities of 20/ 50 in the right eye and 20/ 70 in the left eye, bitemporal visual field loss, and bilateral optic atrophy. General examination revealed skin pallor, hair loss, and an enlarged left axillary lymph node. On direct questioning the patient reported that the latter had been present for 12 years. Endocrine assessment demonstrated panhypopituitarism with diabetes insipidus but a normal prolactin level. His full blood count, urea, and electrolytes, and plasma proteins were normal. Radiological examination included a skull radiograph that was normal. Computed tomographic ( Fig. 1A and B) and magnetic resonance ( Fig. 2) scanning along with a basal cisternogram demonstrated an enhancing suprasellar mass, but bilateral carotid angiography and cavernous sinography were also normal. Surgical biopsy of the enlarged axillary lymph node and the suprasellar mass was carried out, the latter through a frontal craniotomy. At operation the optic chiasm was observed to be markedly expanded in the vertical plane with extension of the lesion into the lamina terminalis. Biopsies were taken from the lamina terminalis and the posterior aspect of the chiasm. Histological examination showed that the normal architecture of the lymph node was effaced by sheets of small lymphoid and histiocytic cells. Against this background, multilobulated ReedSternberg cells and mononuclear Hodgkin's cells were easily found. Numerous noncaseating epithelioid cell granulomata were also present ( Fig. 3). The appearances were characteristic of lymphocyte predominant Hodgkin's disease of diffuse type. The suprasellar tissue consisted of a few minute fragments, which were diffusely infiltrated by pleomorphic atypical lymphoid cells and microglial cells. There was concentric deposition of reticulin fibers around blood vessels ( a characteristic feature of cerebral lymphoma). Although typical Hodgkin's cells or Reed- Sternberg cells were not identified, the overall features were regarded as entirely in keeping with cerebral Hodgkin's disease ( Fig. 4). Additionally, an iliac crest marrow trephine biopsy revealed a hypercellular marrow containing aggregates of pleomorphic atypical lymphoid and histiocytic cells against a sclerotic B FIG. 1. Computed tomographic scan demonstrating suprasellar enhancing mass. A, without contrast; B, with contrast. JC/ ill Neuro- ophthalmol. Vol. 10, No. 4, 1990 250 R. M. MCFADZEAN ET AL. FIG. 2. Magnetic resonance scan showing suprasellar mass ( T 2 weighted image). background. There were occasional large lymphoid cells with prominent nucleoli, but classical Reed- Sternberg cells were not identified. The appearances were, however, considered to be characteristic of marrow involvement by Hodgkin's disease. Treatment was by radiotherapy, 1800 rads in nine fractions, and chemotherapy, a combination of vinblastine, chlorambucil, procarbazine, and prednisolone. Unfortunately, after 11 days he developed a severe pancytopenia and chest infection. Immunosuppression had to be withdrawn and his infection was treated with cephradine, Septrin, and ketoconazoIe, but he failed to respond and died shortly afterward. Postmortem examination revealed an extensive lymphadenopathy involving the left axillary, paraaortic, and peripancreatic regions, but histologically these lymph glands were diffusely replaced by acellular fibrous tissue containing scattered small lymphoid cells. Viable lymphoma was not identified. The bone marrow was hypocellular with foci of necrosis, but again no evidence of residual lymphoma W, l" fl) lI nd, Thl:' appearance of the Ivmph nod,>. ,',,' lei h. ' 1' 1<.' ":" Hrll\ V was consistent / dl// ,.. " with the effect of chemotherapy on Hodgkin's disease. The brain was large without abnormality of the convexities of the cerebral hemispheres or leptomeninges. However, the optic chiasm and lower end of the hypothalamus appeared surrounded by gelatinous tissue ( Fig. 5), with ~ attening an~ discoloration of the mamillary bodIes. HIstologICally the hypothalamus and optic chiasm were repl~ ced by collagenous tissue containing numero~ s fIbroblast- like cells and large numbers of ectatic small vessels, many with thickened hyaline walls, with occasional small foci of necrosis ( Fig. 6). Surrounding this abnormal tissue was a zone of gliosed cerebral parenchyma containing numerous gemistocytic astrocytes, including large and binucleate forms. No residual tumor was present and the appearance was regarded as consistent with therapeutic irradiation. The liver was normal but the spleen showed hypoplasia of the white pulp. There was extensive bilateral generalized bronchopneumonia and death was considered due to a combination of sepsis secondary to aplastic anemia and aspiration bronchopneumonia. DISCUSSION This patient's presentation with progressive loss of vision is rare in Hodgkin's lymphoma. The visual findings and associated endocrine features indicated an intracranial lesion involving the optic chiasm. The endocrine features of diabetes insipidus and panhypopituitarism with a normal prolactin level suggested craniopharyngioma or hypothalamic tumor. Decreased libido, impotence, reduced energy, and symptoms of diabetes insipidus are typical of a craniopharyngioma ( 24,25), and the commonest hormonal deficiencies are in the serum levels of growth hormone, cortisol, and thyroid stimulating hormone, with an elevation of the serum prolactin that is always less than 200 I- lg/ ml ( 25,26). Astrocytomas of the hypothalamus are more common in childhood and adolescence ( 9). The radiological findings, although localizing the intracranial lesion to the suprasellar system, did not provide more diagnostic information, but the combined ophthalmological- endocrinologicaIradiological picture suggested a preoperative diagnosis of a craniopharyngioma. However, the presence of Hodgkin's lymphoma in an axillary lymph node and iliac crest marrow biopsies raised the possibility of a similar lesion at the optic chiasm. Histologically verified Hodgkin's lymphoma affecting the optic chiasm has only previouslv been reported on two occasions ( 19,20), both diclS:: ' sed at autopsy, although in the second case a bi~) i." . of HODGKIN'S DISEASE AT THE OPTIC CHIASM 251 FIG. 3. Axillary lymph node with a binucleate Reed- Sternberg cell ( narrow arrow) and a mononuclear Hodgkin's cell ( broad arrow) in a background of smaller lymphoid and histiocytic cells. Hand E, x125. a thickened optic nerve about 7 months prior to death showed typical Reed- Sternberg cells on postmortem review. Optic nerve involvement with severe visual loss and bilateral optic atrophy has been described in a case of Hodgkin's lymphoma diagnosed by cervical lymph node biopsy with bilateral disc swelling and white peripapillary subretinal exudates at the onset ( 18). A right homonymous hemianopia was noted in a 16- year- old girl with a left parieto-occipital lesion in whom Hodgkin's disease had been diagnosed 2 years previously by a cervical lymph node biopsy ( 21). Visual loss in Hodgkin's disease may be due not only to intracranial causes but also ocular and orbital involvement. Associated ocular conditions include uveitis and retinopathy ( 27- 30), keratitis sicca with bilateral parotid gland enlargement ( 31), and keratitis with vascularization ( 32- 34). Orbital disease is usually secondary and consists of infil- FIG. 4. Suprasellar biopsy showing cellular infiltrate of atypical pleomorphic lymphoid cells. Hand E, x 125. JClin Neuro- ophthalmol, Vol, 10, No. 4, 1990 252 R. M. MCFADZEAN ET AL. FIG. 5. Coronal section through optic chiasm. which is surrounded by gelatinous tissue. tration of the eyelids, subconjunctival space, soft tissues of the orbit, and lacrimal gland ( 35- 37). Rarely, the orbital signs appear primary ( 38). Complications of Hodgkin's disease may potentially cause visual dysfunction including superinfections, such as cryptococcal meningitis, aspergillosis, cytomegalic inclusion disease, and herpes zoster, as a consequence of debilitation and immunosuppression ( 39~ 1) and progressive multifocal leukoencephalopathy ( 42,43). Paraneoplastic disorders may develop, in particular encephalomyelitis, whose effects on the brain stem may cause diplopia and oscillopsia with vestibular nystagmus, unilateral or bilateral horizontal gaze paresis, internuclear ophthalmoplegia, and skew deviation ( 44). Mesencephalic involvement is characterized by ptosis, conjugate or disconjugate vertical gaze paresis, and abnormal involuntary movements ( 45,46). Primary position vertical nystagmus, ataxia, and hypophonic speech may be the first signs of a pareneoplastic cerebellar encephalitis ( 47). Visual symptoms of amaurosis fugax and fortification spectra have been described in young patients regarded as cured cases of Hodgkin's disease and attributed to transient ischemia ( 48) or complicated migraine ( 49). The result of treatment in this case was disap- FIG. 6. Hypothalamus ( postmortem) showing replacement of the normal structure by collagenous tissue containing thick- walled ectatic small vessels and scattered lymphocytes and fibroblasts. Martius- Scarlet- Blue, x32. HODGKIN'S DISEASE AT THE OPTIC CHIASM 253 pointing: There was no remission in symptoms or signs in spite of chemotherapy and radiotherapy. The clinical presentation with lesions in the suprasellar region, one axillary lymph node, and bone marrow suggested stage IV disease ( 50,51). The prognosis for patients with treated stage III to IV Hodgkin's disease is a 10 year survival rate of 60 to 80% ( 41,51,52), but it appeared that this patient died from overwhelming infection with bilateral bronchopneumonia in the presence of debilitation and immunosuppression. The sites of Hodgkin's involvement were all inactive at autopsy. This case and conclusions derived from it merit attention on several grounds. First, direct involvement of the optic chiasm by Hodgkin's disease is very rare but may give rise to visual loss as a presenting sign. Second, in the presence of a potentially treatable condition the importance of obtaining a tissue diagnosis from an unusual chiasmal lesion is apparent. Last, the tissue obtained may show equivocal changes and the final diagnosis requires confirmation from other systemic features. Acknowledgment: We thank Professor G. M. Teasdale, University Department of Neurosurgery, Dr. E. Teasdale, Department of Neuroradio! ogy, and Professor J. H. Adams, University Department of Neuropathology, at the Institute of Neurological Sciences at Glasgow for their helpful assistance with this case. We also thank Mrs. M. Smith for preparation of the manuscript. REFERENCES 1. Wilks S. Cases of lardaceous disease and some allied infections with records. Guy's Hosp Rep 1856; 3: 103- 32. 2. Murchison C. Case of " lymphadenoma" of the lymphatic system, spleen, liver, lungs, heart, diaphragm, dura mater, etc. Trans Path Soc London 1870; 21: 372- 89. 3. Williams HM, Diamond HD, Craver LF, et al. Neurological complications of lymphomas and leukemias. Springfield, IL: Charles C. Thomas, 1959: 3- 7. 4. Ljungdahl I, Strang R, Tovi D. Intracerebral Hodgkin's granuloma: report of a case and review of the literature. Neurochirurgia 1965; 8: 113- 8. 5. Sapozink MD, Kaplan HS. Intracranial Hodgkin's disease: a report of 12 cases and review of the literature. Cancer 1983; 52: 1301- 7. 6. Marshall G, Roesmann U, van den Noort S. Invasive Hodgkin's disease of the brain: report of two new cases and review of American and European literature WIth clinIcalpathologic correlations. Cancer 1968; 22: 621- 30. 7. Griffin JW, Thompson RW, Mitchinson MJ, et al. Lymphomatous lepto- meningitis. Am JMed 1971; 51: 200- 8. 8. Alvarez F, Roda JM, Anciones B, et al. IntracranIal Hodgkin's disease: report of two cases. J Neurosurg Sci 1985; 29: 273- 7. 9. Miller NR. Walsh and Hoyt's Clinical neuro- ophthalmology; vol 3. 4th ed. Baltimore: Williams and Wilkins, 1988: 1589. 10. Constans JP, Castresana A, Meder JF, et a!. Localisations intracraniennes de la maladie de Hodgkin. A propos de deux cas. Bull Cancer 1989; 76: 301- 10. 11. Sparling HJ, Adams RD. Primary Hodgkin's sarcoma of the brain. Arch PathoI1946; 42: 338- 44. 12. Schricker JL Jr, Smith DE. Primary intracerebral Hodgkin's disease. Cancer 1955; 8: 629- 33. 13. Burstein SD, Kernohan JW, Vihelein A. Neoplasms of the reticulo- endothelial system of the brain. Cancer 1963; 16: 289- 305. 14. Cambier J, Boivin P, Giraud A, et al. Les determinations cerebrales de la maladie de Hodgkin. Ann Med Interne 1973; 2: 65- 74. 15. Serebrjanik B. Lymphogranulomatose meningoencephalitis and polyreticulitis. Dtsch Z Nervenheilkd 1933; 129: 103- 30. 16. Vogel PJ, Richland KJ. Involvement of the central nervous system by Hodgkin's disease: case report with five year interval between primary spinal and cerebral lesions. Bull Los Angeles Neurol Soc 1955; 20: 83- 6. 17. Ashby MA, Barber PC Holmes AE, et al. Primary intracranial Hodgkin's disease: a case report and discussion. Am J Surg PathoI1988; 12: 294- 9. 18. Kraus AM, O'Rourke J. Lymphomatous optic neuritis. Arch OphthalmoI1963; 70: 173- 5. 19. Litvak J, Leder MM, Kauvar AJ. Hodgkin's disease involving optic nerve and brain. JNeurosurg 1964; 21: 798- 801. 20. Miller NR, Iliff WJ. Visual loss as the initial symptom in Hodgkin's disease. Arch Ophthalmol 1975; 93: 115~ 1. 21. Biran S, Herishianu Y. Brain involvement in Hodgkin's disease: report of a case. Eur Neurol 1972; 8: 352- 8. 22. Russell DC Rubinstein LJ. Pathology of tumours of the nervous system. 4th ed. London: Edward Arnold, 1977: 104. 23. Adams JH, Graham DI. An introduction to neuropathology. Edinburgh: Chruchill Livingstone, 1988: 254. 24. Kapcala LP, Molitch ME, Post KD, et a!. Galactorrhoea, oligo/ amenorrhoea and hyperprolactinaemia in patients with craniopharyngiomas. JClin Endocrinol Metab 1980; 51: 798- 800. 25. Barreca T, Perria C Francaviglia N, et a!. Evaluation of anterior pituitary function in adult patients with craniopharyngiomas. Acta Neurochir 1984; 71: 263- 72. 26. Jenkins JS, Gilbert q, Ang V. Hypothalamic- pituitary function in patients with craniopharyngiomas. JClin Endocrinol Metab 1976; 43: 394- 9. 27. Hegner CA. Retinitis exudativa bei lymphogranulomatosis. Klin Monatsbl Augenheilkd 1916; 57: 27- 48. 28. Marquardt R. Augenveranderungen bei maliquer lymphogranulomatose ( Morbus Hodgkin). Klin Monatsbl Augenheilkd 1961; 138: 535- 44. 29. Primbs GB, Monsees WE, Irvine AR. Intraocular Hodgkin's disease. Arch OphthalmoI1961; 66: 477- 82. 30. Walsh FB, Hoyt WF. Clinical Neuro- ophthalmology; vol 3. 3rd ed. Baltimore: Williams and Wilkins, 1969: 2304. 31. Kaufman SI. Mikulicz' syndrome. An early manifestation of Hodgkin's disease. Eye Ear Nose Throat Mouth 1950; 29: 257- 8. 32. Matteucci P. Corneal lesions in Hodgkin's disease. Am J Ophthalmol 1947; 30: 126- 42. 33. Francia C. Cheratite in morbo di Hodgkin. Rnss Ital Ottal 1950; 19: 140- 50. 34. Renard G, Haye C. Les manifestations oculaire de la maladie de Hodgkin. Arch Ophtalmol 1956; 16: 601- 14. 35. Watillon M, Prijot E, Farra M. Maladie de Hodgkin, localisation lacrimale. Arch OphtalmoI1964; 24: 153- 5. 36. Duke- Elder S, MacFaul PA. System of ophthalmology; vol 13. London: Henry Kimpton, 1974: 482- 7; 664- 8; 1080- 1. 37. Fratkin JD, Shammas HF, Miller SD. Disseminated Hodgkin's disease with bilateral orbital involvement. Arch Ophthaimol 1978; 96: 102- 4. 38. Reese AB. Tumors of the eye. 3rd ed. New York: Harper and Row, 1976: 389- 91. 39. Williams HM, Diamond HD, Craver LF, et a!. Neurological complications of lymphomas and leukemias. Springfield, IL: Charles C. Thomas, 1959: 115- 26. 40. Ultmann JE, Moran EM. Hodgkin's disease: clinical course and complications. Arch Intern Med 1973; 131: 311- 53. 41. Haskell CM, Parker RG. Hodgkin's disease. In: Haskell J Clin Neuro- ophthalmol, Vol. 10, No. 4, 1990 254 R. M. MCFADZEAN ET AL. CM, ed. Cancer treatment. 2nd ed. Philadelphia: W. B. Saunders, 1985: 758- 88. 42. Astrom K- E, Mancall EL, Richardson EP. Progressive multifocalleukoencephalopathy: a hitherto unrecognised complication of chronic lymphatic leukaemia and Hodgkin's disease. Brain 1958; 81: 9:>- 11l. 43. Krupp LB, Lipton RB, Swerdlow ML, et al. Progressive multifocal leukoencephalopathy: clinical and radiographic features. Ann Neurol 1985; 17: 344- 9. 44. Miller NR. Walsh and Hoyt's Clinical neuro- ophthalmology; vol 3. 4th ed. Baltimore: Williams and Wilkins, 1988: 171l. 45. Henson RA, Russell DS, Wilkinson M. Carcinomatous neuropathy and myopathy: a clinical and pathological study. Brain 1954; 77: 82- 12l. 46. Dorfman LJ, Forno LS. Paraneoplastic encephalomyelitis. Acta Neurol Scand 1972; 48: 556- 73. 47. Saul RF, Towfighi J. Primary position vertical nystagmus, ataxia, and hypophonic speech: a subacute progressive triad of paraneoplastic cerebellar degeneration. C~ ic~ pathologic correlation in three cases. Neurology 1987,37.( 5 1): 304- 5. . . 48. Feldman E, Posner JB. Episodic neurologic dysfunctiOn m patients with Hodgkin's disease. Arch NeuroI1986; 43: 1227- 33. 49. Dulli DA, Levine RL, Chun RW, et al. MigrainOUS neurologic dysfunction in Hodgkin's disease. Arch Neurol 1987; 44: 689. 50. De Vita VT Jr, Hellmann S. Hodgkin's disease and the nonHodgkin's lymphomas. In: De Vita VT Jr, Hellmann 5, Rosenberg SA, eds. Cancer principles and practice of oncology. Philadelphia: J. B. Lippincott, 1982: 1331- 14Ol. 51. Behrens BC, Young RC, De Vita V. Current management of Hodgkin's disease. Drugs 1985; 30: 355- 67. 52. del Regato JA, Spjut HJ, COX JD. Ackerman and del Regato's Cancer: Diagnosis, treatment, and prognosis. 6th ed. St. Louis: C. V. Mosby, 1985: 968- 93. |