The Journal of Laryngology and Otology April 1979. Vol. 93. pp. 413-415
Cranial nerve involvement in malignant lymphoma By G. ROSEN
THE recent successful improvement in the chemotherapy of malignant lymphomas has changed the natural history of these diseases. The remission rate has increased and more of these patients are now seen with central nervous system involvement. Usually nervous system disorders are a late complication and previously reported cases had well established malignant lymphoma. The following is a very rare case report because central nervous system involvement was the presenting manifestation of this disease. Case report A 5.1-year-old man was referred to this department in November 1975 with dysphagia, excessive accummulation of saliva and marked hoarseness. During the period of initial investigation he developed a right facial paralysis with very poor facial muscle tone and absent muscle responses on facial nerve excitability testing. In addition there was a right sensorineural hearing loss. Two weeks later he developed a sixth nerve paralysis. His general condition deteriorated rapidly and he was admitted to a general medical ward, by which time he had bilateral sixth and seventh nerve paralyses and a horizontal nystagmus. He then developed a paralysis of the soft palate necessitating parenteral feeding. The clinical picture was now one of paralysis of the fifth, sixth, seventh, eighth, ninth and tenth cranial nerves bilaterally, a right hemiparesis and a horizontal nystagmus. Meningeal involvement was not apparent. Apart from these neurological signs there was little else evident on general examination other than a palpable liver. Neither lymph nodes nor spleen were palpable. Peripheral blood tests were normal and chest X-ray, intravenous pyelogram and liver, spleen, thyroid and kidney scans were also unremarkable. There was a raised protein of 350 mgm per cent in the c.s.f. which was otherwise normal. A bone scan showed increased localized uptake in the tenth thoracic and fourth and fifth lumbar vertebrae and the right petrous temporal bone. A brain scan showed increased midline uptake. Bone marrow studies revealed malignant lymphoma cells and the same cells were also found in the c.s.f. A diagnosis of malignant lymphoma was made and the patient was then treated with COP (Cytophosphan 800 mg/day, Oncovine 1-5 mg/day and Prednisolone 60 mg/day) together with Adriamicin 40 mg/day. At a later stage Methotrexate 10 mg intrathecally was given. There was good response to this treatment and the cranial nerve paralyses recovered so that swallowing no longer was a problem, the hoarseness improved, the facial paralyses disappeared and audiometry demonstrated normal hearing. It had been impossible because of the patient's ill health to establish whether this deafness had been cochlear or retrocochlear. 413
414
G. ROSEN
Since recovery the patient has received cyclic treatment with COP, Adriamicin and intrathecal Methotrexate. His condition has remained satisfactory and stable for the 14 months since treatment started. Comment
Malignant lymphoma normally presents with cervical lymph node swelling, splenic enlargement and anaemia. Exceptions have been reported and these include the solitary lymphoma of the neck or of the larynx. Rarer still is that presenting initially with central nervous system involvement. Sando and colleagues (1969) found recorded only two histopathological reports of temporal bone infiltration by malignant lymphoma and to these they added a third. Paparella and El Fiky (1972) documented eight more cases, and Palva and colleagues (1974) reported another patient with this condition. In all these patients central nervous system involvement was evident in the later stages of the disease or at autopsy. Palva's report was of a lymphoblastic lymphosarcoma and facial nerve paralysis, and post mortem examination showed a leptomeningeal infiltration that extended to the facial and auditory nerves. Although both nerves were heavily infiltrated, only the facial nerve was clinically affected. Sando described a similar patient with invasion of the seventh and eighth nerves without clinical evidence of this. In Paparella and El Fiky's series only one of the eight patients had heavy infiltration of the facial nerve with consequent loss of function. In the other patients there was no apparent disturbance of function although the nerves were infiltrated by tumour cells. Nerve dysfunction in malignant lymphoma can be due to: (1) direct pressure on the nerve from the adjacent enlarged lymph nodes; (2) nerve infiltration by tumour cells; and (3) a true neuropathy. Autopsy reports suggest the second of these possibilities to be the most likely. Malignant infiltration, which is mainly around the nerve bundles, progresses rapidly along the nerves. Extensive infiltration is observed where these.nerves pass through their bony canals (cribiform plate, habenula perforata). Only rarely are the nerve fibres actually destroyed with disappearance of the axon cylinders and the Schwann cell nuclei. Whether these pathological changes are the result of compression of the nerve by invading tumour cells or by invasion of the vascular supply to the nerve by tumour cells is unknown. The extent of meningeal infiltration seen on autopsy was far larger than that anticipated on clinical grounds. It does not explain why there was an abundance of clinical signs in our case nor does it explain their subsequent rapid resolution on treatment. It would appear that metastatic infiltration of these nerves can be eliminated by chemotherapy, and three patients reported by Griffin and colleagues (1971) were treated with intrathecal methotrexate and radiotherapy. At autopsy no meningeal lymphoma was found. There is a close correlation between central nervous system and bone marrow involvement. Griffin found marrow involvement in 100 per cent of patients with lymphomatous leptomeningitis at autopsy. In the report by Burn and colleagues (1976), nearly all patients with this complication had preceding bone marrow involvement. According to Rubinstein (1969), the development of cranial nerve palsies is usually an ominous sign. It invariably occurred during the progressive
CLINICAL RECORDS
415
stage of the disease and the mean duration of life after a cranial nerve palsy develops was only 3 months. The mode of tumour spread to the leptomeninges is controversial and a number of possibilities exist, namely by way of the perivascular or the perineural lymphatics or via the blood stream. Tumour infiltration was most extensive in the posterior cranial fossa and, according to Oshiro and Perleman (1965), there appears to be a predilection for spread of these subarachnoid tumour cells into the internal auditory meati, the reasons for which are not clear. Summary
A rare case of malignant lymphoma extensively invading the central nervous system is presented. Cranial nerve involvement is usually a late complication of this disease and its presentation is an ominous sign. This patient presented with symptoms and signs related to the fifth to tenth cranial nerves inclusive. He responded promptly to chemotherapy and has been followed up for 14 months without recurrence. REFERENCES BURN, P. A. et al. (1976) Blood, 47, 3. GRIFFIN, J. W. et al. (1971) The American Journal of Medicine, 51, 200. OSHIRO, H., and PERLEMAN, H. B. (1965) Archives of Oto-Rhino-Laryngology, 81, 328. PALVA, T. et al. (1974) Archives of Oto-Rhino-Laryngology, 99, 733. PAPARELLA, M. M., and EL FIKY, F. M. (1972) Annals of Otology, Rhinology and Laryngology, 81, 352. RUBINSTEIN, M. R. (1969) Annals of Internal Medicine, 70, 49. SANDO, I. et al. (1969) Laryngoscope, 79, 2140. Department of Otolaryngology, Central Emek Hospital, Afula, Israel
Cranial nerve involvement in malignant lymphoma By G. ROSEN
THE recent successful improvement in the chemotherapy of malignant lymphomas has changed the natural history of these diseases. The remission rate has increased and more of these patients are now seen with central nervous system involvement. Usually nervous system disorders are a late complication and previously reported cases had well established malignant lymphoma. The following is a very rare case report because central nervous system involvement was the presenting manifestation of this disease. Case report A 5.1-year-old man was referred to this department in November 1975 with dysphagia, excessive accummulation of saliva and marked hoarseness. During the period of initial investigation he developed a right facial paralysis with very poor facial muscle tone and absent muscle responses on facial nerve excitability testing. In addition there was a right sensorineural hearing loss. Two weeks later he developed a sixth nerve paralysis. His general condition deteriorated rapidly and he was admitted to a general medical ward, by which time he had bilateral sixth and seventh nerve paralyses and a horizontal nystagmus. He then developed a paralysis of the soft palate necessitating parenteral feeding. The clinical picture was now one of paralysis of the fifth, sixth, seventh, eighth, ninth and tenth cranial nerves bilaterally, a right hemiparesis and a horizontal nystagmus. Meningeal involvement was not apparent. Apart from these neurological signs there was little else evident on general examination other than a palpable liver. Neither lymph nodes nor spleen were palpable. Peripheral blood tests were normal and chest X-ray, intravenous pyelogram and liver, spleen, thyroid and kidney scans were also unremarkable. There was a raised protein of 350 mgm per cent in the c.s.f. which was otherwise normal. A bone scan showed increased localized uptake in the tenth thoracic and fourth and fifth lumbar vertebrae and the right petrous temporal bone. A brain scan showed increased midline uptake. Bone marrow studies revealed malignant lymphoma cells and the same cells were also found in the c.s.f. A diagnosis of malignant lymphoma was made and the patient was then treated with COP (Cytophosphan 800 mg/day, Oncovine 1-5 mg/day and Prednisolone 60 mg/day) together with Adriamicin 40 mg/day. At a later stage Methotrexate 10 mg intrathecally was given. There was good response to this treatment and the cranial nerve paralyses recovered so that swallowing no longer was a problem, the hoarseness improved, the facial paralyses disappeared and audiometry demonstrated normal hearing. It had been impossible because of the patient's ill health to establish whether this deafness had been cochlear or retrocochlear. 413
414
G. ROSEN
Since recovery the patient has received cyclic treatment with COP, Adriamicin and intrathecal Methotrexate. His condition has remained satisfactory and stable for the 14 months since treatment started. Comment
Malignant lymphoma normally presents with cervical lymph node swelling, splenic enlargement and anaemia. Exceptions have been reported and these include the solitary lymphoma of the neck or of the larynx. Rarer still is that presenting initially with central nervous system involvement. Sando and colleagues (1969) found recorded only two histopathological reports of temporal bone infiltration by malignant lymphoma and to these they added a third. Paparella and El Fiky (1972) documented eight more cases, and Palva and colleagues (1974) reported another patient with this condition. In all these patients central nervous system involvement was evident in the later stages of the disease or at autopsy. Palva's report was of a lymphoblastic lymphosarcoma and facial nerve paralysis, and post mortem examination showed a leptomeningeal infiltration that extended to the facial and auditory nerves. Although both nerves were heavily infiltrated, only the facial nerve was clinically affected. Sando described a similar patient with invasion of the seventh and eighth nerves without clinical evidence of this. In Paparella and El Fiky's series only one of the eight patients had heavy infiltration of the facial nerve with consequent loss of function. In the other patients there was no apparent disturbance of function although the nerves were infiltrated by tumour cells. Nerve dysfunction in malignant lymphoma can be due to: (1) direct pressure on the nerve from the adjacent enlarged lymph nodes; (2) nerve infiltration by tumour cells; and (3) a true neuropathy. Autopsy reports suggest the second of these possibilities to be the most likely. Malignant infiltration, which is mainly around the nerve bundles, progresses rapidly along the nerves. Extensive infiltration is observed where these.nerves pass through their bony canals (cribiform plate, habenula perforata). Only rarely are the nerve fibres actually destroyed with disappearance of the axon cylinders and the Schwann cell nuclei. Whether these pathological changes are the result of compression of the nerve by invading tumour cells or by invasion of the vascular supply to the nerve by tumour cells is unknown. The extent of meningeal infiltration seen on autopsy was far larger than that anticipated on clinical grounds. It does not explain why there was an abundance of clinical signs in our case nor does it explain their subsequent rapid resolution on treatment. It would appear that metastatic infiltration of these nerves can be eliminated by chemotherapy, and three patients reported by Griffin and colleagues (1971) were treated with intrathecal methotrexate and radiotherapy. At autopsy no meningeal lymphoma was found. There is a close correlation between central nervous system and bone marrow involvement. Griffin found marrow involvement in 100 per cent of patients with lymphomatous leptomeningitis at autopsy. In the report by Burn and colleagues (1976), nearly all patients with this complication had preceding bone marrow involvement. According to Rubinstein (1969), the development of cranial nerve palsies is usually an ominous sign. It invariably occurred during the progressive
CLINICAL RECORDS
415
stage of the disease and the mean duration of life after a cranial nerve palsy develops was only 3 months. The mode of tumour spread to the leptomeninges is controversial and a number of possibilities exist, namely by way of the perivascular or the perineural lymphatics or via the blood stream. Tumour infiltration was most extensive in the posterior cranial fossa and, according to Oshiro and Perleman (1965), there appears to be a predilection for spread of these subarachnoid tumour cells into the internal auditory meati, the reasons for which are not clear. Summary
A rare case of malignant lymphoma extensively invading the central nervous system is presented. Cranial nerve involvement is usually a late complication of this disease and its presentation is an ominous sign. This patient presented with symptoms and signs related to the fifth to tenth cranial nerves inclusive. He responded promptly to chemotherapy and has been followed up for 14 months without recurrence. REFERENCES BURN, P. A. et al. (1976) Blood, 47, 3. GRIFFIN, J. W. et al. (1971) The American Journal of Medicine, 51, 200. OSHIRO, H., and PERLEMAN, H. B. (1965) Archives of Oto-Rhino-Laryngology, 81, 328. PALVA, T. et al. (1974) Archives of Oto-Rhino-Laryngology, 99, 733. PAPARELLA, M. M., and EL FIKY, F. M. (1972) Annals of Otology, Rhinology and Laryngology, 81, 352. RUBINSTEIN, M. R. (1969) Annals of Internal Medicine, 70, 49. SANDO, I. et al. (1969) Laryngoscope, 79, 2140. Department of Otolaryngology, Central Emek Hospital, Afula, Israel
