Journal of Neuro-Ophthalmology, December 1990, Volume 10, Issue 4

Hodgkin's disease at the optic chiasm.

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.

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. 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