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Chromophobe Adenoma Masquerading As Corticosteroid-Responsive Optic Neuritis
CHROMOPHOBE ADENOMA MASQUERADING AS CORTICOSTEROID-RESPONSIVE OPTIC N E U R I T I S RICHARD C. SENELICK, M.D.,
AND HENRY J. L. V A N DYK,
M.D.
Salt Lake City, Utah 1
In 1966 Cogan cautioned that, "Prob ably no branch of neuro-ophthalmology has to its discredit the abundance of erroneous diagnoses as has optic neuritis." Pituitary neoplasms, particularly those presenting with atypical field defects, probably lead the list of tumors that initially simulate op tic neuritis. 2 ' 3 This simulation is enhanced when visual acuity and/or visual field de fects of the patient improve with systemic corticosteroid therapy. Usually, however, the improvement in visual function in pa tients with tumors is not great, nor is it prolonged. Knight, Hoyt, and Wilson4 re cently noted that the majority of patients with optic nerve compression by tumor are treated with corticosteroids at some point, but the improvement of visual function is not sustained. We recently saw a patient whose visual loss underwent a striking and sustained im provement concomitant with the adminis tration of systemic corticosteroids, thus de laying the diagnosis of a chromophobe ade noma for 18 months. CASE REPORT A 32-year-old white man was referred to the University of Utah Medical Center for evalua tion of a bitemporal hemianopsia. Eighteen months earlier he had first noted blurred vision in both eyes. A week later, on Dec. 14, 1970, an ophthalmologist found best corrected visual acuity to be 20/200 with the right eye and 20/100 with the left eye. Retrobulbar neuritis was the clini cal impression, and the patient was given A C T H , 80 units daily by intramuscular injection for six From the Department of Neurology and the Division of Ophthalmology, University of Utah Medical Center, Salt Lake City, Utah. This study was supported in part by training grant 5T01 N S 5309 from the National Institutes of Health and by the Eleanor Roosevelt Cancer Foundation Re search Institute. Reprint requests to Henry J. L. Van Dyk, M.D., Division of Ophthalmology, 50 N. Medical Dr. Salt Lake City, U T 84132.
doses, with mild visual improvement. Visual fields on the sixth day were reported to show a small superior temporal defect in the right eye only. On Dec. 30, he was hospitalized and treated with A C T H , 40 units by intravenous drip daily for five days. Skull x-ray films, brain scan, electro encephalogram, and lumbar puncture were nor mal, and a neurosurgical consultant agreed with the diagnosis of retrobulbar neuritis. Examination on Jan. 15, 1971, disclosed that his visual acuity had improved to 20/30— with the right eye and 20/30 + 2 with the left eye. By Jan. 27, visual acuity of 20/20— was recorded in each eye. Acuity then remained stable without further treatment until June 1972, when the pa tient again noted blurred vision. Examination by a second ophthalmologist revealed a best cor rected visual acuity of 20/40 with the right eye and 20/60 — 2 with the left eye, with a dense bitemporal hemianopsia. The patient was re ferred to U U M C . Examination on June 11 revealed an acuity of 20/25— with the right eye and 20/30+ with the left eye. Pupillary reflexes were normal without afferent defects. Color vision was normal, and visual field testing indicated a bitemporal hemi anopsia (Fig. 1). T h e remainder of the ophthal mic examination was normal. Neurologic, neuro surgical, and endocrinologic consultants were un able to detect other abnormalities. Skull x-ray series with polytomes of the sella turcica, brain scan, and blood and urine analyses were unremarkable. A lumbar puncture showed a normal pressure and a cerebrospinal fluid pro tein level of 74 mg/100 ml. A transfemoral se lective right carotid arteriogram was normal. A pneumoencephalogram with polytomes of the an terior third ventricle (Figs. 2 and 3) demonstrated a large suprasellar mass indenting and displac ing the anterior third ventricle. The mass was eccentric, being larger on the right side. Neurosurgical exploration was performed through a right frontal craniotomy (Dr. Theo dore Roberts). On elevation of the right frontal lobe, a large bluish cystic-appearing mass was visualized, principally underlying the right optic nerve. This was incised and drained of 10 ml of brownish bloody fluid. T h e solid portion of the mass was then excised. Histopathologic diag nosis was chromophobe adenoma. Two months postoperatively his visual acuity was 20/20 bilaterally with full visual fields. DISCUSSION
T h e m i s d i a g n o s i s of p i t u i t a r y is still a c o m m o n 485
neoplasms
occurrence. I n a
series
AMERICAN JOURNAL OF OPHTHALMOLOGY
486 120
90
75
120
60
105
90
75
SEPTEMBER, 1974 60
6Q 5Q
150/
43 29 165£.
180
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240
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70 270
'315 285
300
RIGHT
Fig. 1 (Senelick and Van Dyk). Visual field, June 11, 1972, with Goldmann perimeter (IV-4, 1-2, 1-1), demonstrating a bitemporal hemianopsia of 30 cases of pituitary neoplasms, not one was correctly diagnosed when first seen. 5 Once the diagnosis of optic neuritis is made, the clinician may become suspicious when an atypical field defect is found or there is a failure to improve. T h e occur rence of hemianopic defects or paracentral hemianopic scotomas should suggest an
other explanation for the visual loss. T h e early occurrence of a superior temporal de fect in the present case prompted the re ferring ophthalmologist to obtain a series of laboratory studies. However, the nega tive results of these initial studies, coupled with the patient's striking improvement on
Fig. 2 (Senelick and Van Dyk). Pneumoen cephalogram demonstrating marked indentation of the anterior third ventricle by a large suprasellar mass.
Fig. 3 (Senelick and Van Dyk). Anteroposterior pneumoencephalogram demonstrating air in the displaced anterior third ventricle (arrow) lying on top of the mass.
VOL. 78, NO. 3
CHROMOPHOBE ADENOMA
systemic corticosteroids, gave the clinician a false sense of security, and resulted in a failure to perform serial visual field exami nations. A particularly interesting aspect of the present case was the striking and sustained improvement in visual acuity during and after systemic corticosteroid therapy. The operative findings suggest an interesting ex planation for this patient's course. The large cystic mass contained a mixture of old blood and brown grumous material. Histologic sections revealed a classic sinus oidal chromophobe adenoma with areas of hemorrhage. Cystic changes are not un common in pituitary adenomas and are found in 17% of all pituitary neoplasms.6 The formation of these cystic cavities is thought to result from rapid growth of the tumor outstripping its vascular supply and resulting in local degeneration and hemor rhage. This may be considered as a form of "subclinical" pituitary apoplexy. A re cent review of the subject suggests that pituitary apoplexy results from impaction
of the neoplasm at the diaphragmatic notch, thus compromising its vascular sup ply.7 In its full-blown form, pituitary apo plexy is a dramatic event that often results in bilateral blindness or death. Meadows8 reported three cases of typical pituitary ap oplexy in which he thought that "spon taneous arrest or even cure of a pituitary adenoma by hemorrhagic infarction" had occurred. With the introduction of cortico steroid therapy, there has been a marked reduction in morbidity and mortality asso ciated with pituitary apoplexy. Several authors 5 ' 8 ' 9 have noted the spon taneous occurrence of improvement in vi sion and field followed later by a failure of vision. Two of these cases presented with other signs of pituitary apoplexy.5 Cushing and Walker 9 attributed these changes to the degree of edema and vascularity in the tumor and its resultant ef fect on nearby visual structures. The present patient most likely experi enced a pituitary hemorrhage that re sponded favorably to systemic cortico-
20/20
VISUAL ACUITY
20/200-
t
t
487
PITUITARY DEGENERATION HEMORRHAGE 12/70 TIME-
CYSTIC SURGERY 6/72 GROWTH
Fig. 4 (Senelick and Van Dyk). Likely course of events.
488
AMERICAN JOURNAL OF OPHTHALMOLOGY
steroid therapy. Consequent degenerative changes may have accounted for his sus tained improvement, but with the progres sion of the resultant cystic growth his symp toms returned (Fig. 4). It is important to restate the need for careful and serial visual field examinations in patients with apparent optic neuritis. Knight, Hoyt, and Wilson4 advocate "neuroradiologic exploration" of patients with unexplained visual loss. The use of oral and retrobulbar corticosteroids Tty ophthal mologists is. a continuing practice in the treatment of optic neuritis^ despite the fact that its efficacy is still controversial. In light of this, we would add to the warn ings of others that a favorable and pro longed response to corticosteroids does not confirm the diagnosis of optic neuritis. SUMMARY
A 32-year-old man was considered to have retrobulbar neuritis. He presented with decreased visual acuity (20/200 with the right eye and 20/100 with the left eye) ; acuity returned to normal (20/20—) after one month of systemic corticosteroid ther apy. With no further treatment, this im provement was sustained for 14 months, when the patient again developed decreased vision. A bitemporal hemianopsia was then found. Pneumoencephalography showed a large suprasellar mass, and a large cystic
SEPTEMBER, 1974
chromophobe adenoma was removed. The patient's visual acuity and fields returned to normal. He probably experienced a pitui tary hemorrhage that responded favorably to systemic corticosteroid therapy. A pro longed improvement of visual function in response to corticosteroid therapy does not confirm the diagnosis of optic neuritis. REFERENCES
1. Cogan, D. G.: Neurology of the Visual Sys tem. Springfield, Charles C Thomas, 1966, p. 157. 2. Schlezinger, N. S., and Thompson, R. A.: Pituitary tumors with central scotomas simulat ing retrobulbar neuritis. Neurology 17:782, 1967. 3. Wilson, P., and Falconer, M.: Patterns of visual failure with pituitary tumors. Br. J. Ophthalmol. 52:94, 1968. 4. Knight, C. L., Hoyt, W. F., and Wilson, C. B.: Syndrome of incipient prechiasmal optic nerve compression. Arch. Ophthalmol. 87:1, 1972. 5. Lyle, K., and Clover, P.: Ocular symptoms and signs in pituitary tumors. Proc. R. Soc. Med. 54:611, 1961. 6. Dott, N., and Bailey, P.: A consideration of the hypophysial adenomata. Br. J. Surg. 13:314, 1925. 7. Rovit, R. L., and Fein, J. M.: Pituitary ap oplexy. A review and appraisal. J. Neurosurg. 37:280, 1972. 8. Meadows, S. P.: Unusual clinical features and modes of presentation in pituitary adenomas, including pituitary apoplexy. In Smith, J. L. (ed.) : Neuro-ophthalmology Symposium of the University of Miami, vol. 4. St. Louis, C. V. Mosby, 1968, p. 187. 9. Cushing, H., and Walker, C : Distortion of the visual fields in cases of brain tumor. Brain 37:341, 1915.
AND HENRY J. L. V A N DYK,
M.D.
Salt Lake City, Utah 1
In 1966 Cogan cautioned that, "Prob ably no branch of neuro-ophthalmology has to its discredit the abundance of erroneous diagnoses as has optic neuritis." Pituitary neoplasms, particularly those presenting with atypical field defects, probably lead the list of tumors that initially simulate op tic neuritis. 2 ' 3 This simulation is enhanced when visual acuity and/or visual field de fects of the patient improve with systemic corticosteroid therapy. Usually, however, the improvement in visual function in pa tients with tumors is not great, nor is it prolonged. Knight, Hoyt, and Wilson4 re cently noted that the majority of patients with optic nerve compression by tumor are treated with corticosteroids at some point, but the improvement of visual function is not sustained. We recently saw a patient whose visual loss underwent a striking and sustained im provement concomitant with the adminis tration of systemic corticosteroids, thus de laying the diagnosis of a chromophobe ade noma for 18 months. CASE REPORT A 32-year-old white man was referred to the University of Utah Medical Center for evalua tion of a bitemporal hemianopsia. Eighteen months earlier he had first noted blurred vision in both eyes. A week later, on Dec. 14, 1970, an ophthalmologist found best corrected visual acuity to be 20/200 with the right eye and 20/100 with the left eye. Retrobulbar neuritis was the clini cal impression, and the patient was given A C T H , 80 units daily by intramuscular injection for six From the Department of Neurology and the Division of Ophthalmology, University of Utah Medical Center, Salt Lake City, Utah. This study was supported in part by training grant 5T01 N S 5309 from the National Institutes of Health and by the Eleanor Roosevelt Cancer Foundation Re search Institute. Reprint requests to Henry J. L. Van Dyk, M.D., Division of Ophthalmology, 50 N. Medical Dr. Salt Lake City, U T 84132.
doses, with mild visual improvement. Visual fields on the sixth day were reported to show a small superior temporal defect in the right eye only. On Dec. 30, he was hospitalized and treated with A C T H , 40 units by intravenous drip daily for five days. Skull x-ray films, brain scan, electro encephalogram, and lumbar puncture were nor mal, and a neurosurgical consultant agreed with the diagnosis of retrobulbar neuritis. Examination on Jan. 15, 1971, disclosed that his visual acuity had improved to 20/30— with the right eye and 20/30 + 2 with the left eye. By Jan. 27, visual acuity of 20/20— was recorded in each eye. Acuity then remained stable without further treatment until June 1972, when the pa tient again noted blurred vision. Examination by a second ophthalmologist revealed a best cor rected visual acuity of 20/40 with the right eye and 20/60 — 2 with the left eye, with a dense bitemporal hemianopsia. The patient was re ferred to U U M C . Examination on June 11 revealed an acuity of 20/25— with the right eye and 20/30+ with the left eye. Pupillary reflexes were normal without afferent defects. Color vision was normal, and visual field testing indicated a bitemporal hemi anopsia (Fig. 1). T h e remainder of the ophthal mic examination was normal. Neurologic, neuro surgical, and endocrinologic consultants were un able to detect other abnormalities. Skull x-ray series with polytomes of the sella turcica, brain scan, and blood and urine analyses were unremarkable. A lumbar puncture showed a normal pressure and a cerebrospinal fluid pro tein level of 74 mg/100 ml. A transfemoral se lective right carotid arteriogram was normal. A pneumoencephalogram with polytomes of the an terior third ventricle (Figs. 2 and 3) demonstrated a large suprasellar mass indenting and displac ing the anterior third ventricle. The mass was eccentric, being larger on the right side. Neurosurgical exploration was performed through a right frontal craniotomy (Dr. Theo dore Roberts). On elevation of the right frontal lobe, a large bluish cystic-appearing mass was visualized, principally underlying the right optic nerve. This was incised and drained of 10 ml of brownish bloody fluid. T h e solid portion of the mass was then excised. Histopathologic diag nosis was chromophobe adenoma. Two months postoperatively his visual acuity was 20/20 bilaterally with full visual fields. DISCUSSION
T h e m i s d i a g n o s i s of p i t u i t a r y is still a c o m m o n 485
neoplasms
occurrence. I n a
series
AMERICAN JOURNAL OF OPHTHALMOLOGY
486 120
90
75
120
60
105
90
75
SEPTEMBER, 1974 60
6Q 5Q
150/
43 29 165£.
180
2 0,
8|0 7 0 6l0 510
40 5l0/6l0 6l0
20 \ ^ & \
/
1345
35 210\
40 \ Jb/'
4^
\j y<
60
BO
7330
60
225N 270
285
LEFT
240
255
70 270
'315 285
300
RIGHT
Fig. 1 (Senelick and Van Dyk). Visual field, June 11, 1972, with Goldmann perimeter (IV-4, 1-2, 1-1), demonstrating a bitemporal hemianopsia of 30 cases of pituitary neoplasms, not one was correctly diagnosed when first seen. 5 Once the diagnosis of optic neuritis is made, the clinician may become suspicious when an atypical field defect is found or there is a failure to improve. T h e occur rence of hemianopic defects or paracentral hemianopic scotomas should suggest an
other explanation for the visual loss. T h e early occurrence of a superior temporal de fect in the present case prompted the re ferring ophthalmologist to obtain a series of laboratory studies. However, the nega tive results of these initial studies, coupled with the patient's striking improvement on
Fig. 2 (Senelick and Van Dyk). Pneumoen cephalogram demonstrating marked indentation of the anterior third ventricle by a large suprasellar mass.
Fig. 3 (Senelick and Van Dyk). Anteroposterior pneumoencephalogram demonstrating air in the displaced anterior third ventricle (arrow) lying on top of the mass.
VOL. 78, NO. 3
CHROMOPHOBE ADENOMA
systemic corticosteroids, gave the clinician a false sense of security, and resulted in a failure to perform serial visual field exami nations. A particularly interesting aspect of the present case was the striking and sustained improvement in visual acuity during and after systemic corticosteroid therapy. The operative findings suggest an interesting ex planation for this patient's course. The large cystic mass contained a mixture of old blood and brown grumous material. Histologic sections revealed a classic sinus oidal chromophobe adenoma with areas of hemorrhage. Cystic changes are not un common in pituitary adenomas and are found in 17% of all pituitary neoplasms.6 The formation of these cystic cavities is thought to result from rapid growth of the tumor outstripping its vascular supply and resulting in local degeneration and hemor rhage. This may be considered as a form of "subclinical" pituitary apoplexy. A re cent review of the subject suggests that pituitary apoplexy results from impaction
of the neoplasm at the diaphragmatic notch, thus compromising its vascular sup ply.7 In its full-blown form, pituitary apo plexy is a dramatic event that often results in bilateral blindness or death. Meadows8 reported three cases of typical pituitary ap oplexy in which he thought that "spon taneous arrest or even cure of a pituitary adenoma by hemorrhagic infarction" had occurred. With the introduction of cortico steroid therapy, there has been a marked reduction in morbidity and mortality asso ciated with pituitary apoplexy. Several authors 5 ' 8 ' 9 have noted the spon taneous occurrence of improvement in vi sion and field followed later by a failure of vision. Two of these cases presented with other signs of pituitary apoplexy.5 Cushing and Walker 9 attributed these changes to the degree of edema and vascularity in the tumor and its resultant ef fect on nearby visual structures. The present patient most likely experi enced a pituitary hemorrhage that re sponded favorably to systemic cortico-
20/20
VISUAL ACUITY
20/200-
t
t
487
PITUITARY DEGENERATION HEMORRHAGE 12/70 TIME-
CYSTIC SURGERY 6/72 GROWTH
Fig. 4 (Senelick and Van Dyk). Likely course of events.
488
AMERICAN JOURNAL OF OPHTHALMOLOGY
steroid therapy. Consequent degenerative changes may have accounted for his sus tained improvement, but with the progres sion of the resultant cystic growth his symp toms returned (Fig. 4). It is important to restate the need for careful and serial visual field examinations in patients with apparent optic neuritis. Knight, Hoyt, and Wilson4 advocate "neuroradiologic exploration" of patients with unexplained visual loss. The use of oral and retrobulbar corticosteroids Tty ophthal mologists is. a continuing practice in the treatment of optic neuritis^ despite the fact that its efficacy is still controversial. In light of this, we would add to the warn ings of others that a favorable and pro longed response to corticosteroids does not confirm the diagnosis of optic neuritis. SUMMARY
A 32-year-old man was considered to have retrobulbar neuritis. He presented with decreased visual acuity (20/200 with the right eye and 20/100 with the left eye) ; acuity returned to normal (20/20—) after one month of systemic corticosteroid ther apy. With no further treatment, this im provement was sustained for 14 months, when the patient again developed decreased vision. A bitemporal hemianopsia was then found. Pneumoencephalography showed a large suprasellar mass, and a large cystic
SEPTEMBER, 1974
chromophobe adenoma was removed. The patient's visual acuity and fields returned to normal. He probably experienced a pitui tary hemorrhage that responded favorably to systemic corticosteroid therapy. A pro longed improvement of visual function in response to corticosteroid therapy does not confirm the diagnosis of optic neuritis. REFERENCES
1. Cogan, D. G.: Neurology of the Visual Sys tem. Springfield, Charles C Thomas, 1966, p. 157. 2. Schlezinger, N. S., and Thompson, R. A.: Pituitary tumors with central scotomas simulat ing retrobulbar neuritis. Neurology 17:782, 1967. 3. Wilson, P., and Falconer, M.: Patterns of visual failure with pituitary tumors. Br. J. Ophthalmol. 52:94, 1968. 4. Knight, C. L., Hoyt, W. F., and Wilson, C. B.: Syndrome of incipient prechiasmal optic nerve compression. Arch. Ophthalmol. 87:1, 1972. 5. Lyle, K., and Clover, P.: Ocular symptoms and signs in pituitary tumors. Proc. R. Soc. Med. 54:611, 1961. 6. Dott, N., and Bailey, P.: A consideration of the hypophysial adenomata. Br. J. Surg. 13:314, 1925. 7. Rovit, R. L., and Fein, J. M.: Pituitary ap oplexy. A review and appraisal. J. Neurosurg. 37:280, 1972. 8. Meadows, S. P.: Unusual clinical features and modes of presentation in pituitary adenomas, including pituitary apoplexy. In Smith, J. L. (ed.) : Neuro-ophthalmology Symposium of the University of Miami, vol. 4. St. Louis, C. V. Mosby, 1968, p. 187. 9. Cushing, H., and Walker, C : Distortion of the visual fields in cases of brain tumor. Brain 37:341, 1915.