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Nature and Treatment of Cerebrospinal Fluid Rhinorrhea in Pituitary Tumors
Symposium on Surgical Techniques
Nature and Treatment of Cerebrospinal Fluid Rhinorrhea in Pituitary Tumors
Charles A. Fager, M.D.
Untreated pituitary adenomas seldom produce cerebrospinal fluid rhinorrhea, because the expanding tumor acts as a "stopper." In a search of the literature, only seven proved pituitary neoplasms were found in which cerebrospinal fluid drainage was spontaneous.!, 4, 5, R Other isolated cases have been reported, all following treatment of the tumor either immediately after operation or as a later sequel of radiation or surgery. Ray and Berglund,7 in their paper on rhinorrhea, gave examples of both. Henderson,3 who reported Cushing's series of 338 cases, found 8 patients with a downward extension of the tumor that was so large it actually presented in the nasopharynx. None of these patients had rhinorrhea, and, interestingly enough, no leaks occurred after operation. On reviewing these cases it seems clear that only a small portion of the adenoma was removed, probably because of the dreaded threat of meningitis, so that the large bulk of the tumor still acted as a barrier even though the chiasmal reservoir was opened. This seems to be the important mechanism preventing spontaneous rhinorrhea. Cerebrospinal fluid leakage has always been a well recognized, immediate complication of pituitary surgery especially by previous transsphenoidal types of operations but, in our series at the Lahey Clinic Foundation, the major and persistent instances of rhinorrhea have all occurred as a later complication of treatment. In this regard two factors seem significant. First is our traditional reluctance to perform trans-sphenoidal operations and second is our long-standing interest in radiation therapy, which has successfully been employed for these lesions for many years. It seems possible that necrosis in the thinned-out tumor capsule or dura may be of some importance in the later development of rhinorrhea as a result of the subsequent pulsatile fluid forces at work following treatment. In a series of more than 400 pituitary tumors, this type of late complication has been encountered in 9 patients. All these tumors exhibited some of the variables of pituitary tumors but also, in some ways, conformed to a pattern in their natural and therapeutic courses. Surgical Clinics of North America- Vol. 53, No.2, April 1973
283
284
CHARLES A. FAGER
All these patients presented with a long or moderately long history of slowly growing tumor eroding the sella for many years, not always a particularly invasive neoplasm but in every instance showing a marked downward extension by radiography, obviously involving and usually obliterating the sphenoid sinus (Table 1). Periods of observation ranged from 3 to 36 years among the patients who are deceased (Table 1). The patient who was observed for only 3 years died 6 months after surgery as a result of hydrocephalus after closure of the fistula, this being the only patient in the series in whom treatment did not lead to a successful outcome. Otherwise, this patient would also have had a much longer period of observation. The one among the survivors who has been observed for only 5 years was first seen in 1967. The other 2 patients, who are deceased, died of causes unrelated to their pituitary tumors. Autopsy was performed on the patient who survived for 36 years, and a small amount of residual adenoma was found. All the patients in this group had radiation treatment; 6 underwent surgery as well during the initial treatment of the pituitary adenoma (Table 1). Some of the earlier patients in the series received conventional radiation therapy to the region of the pituitary fossa. The patients treated since 1950 were given 2 Mev radiation therapy by a rotational method as previously described with a tumor dose of '4000 R delivered to the region of the pituitary tumor throug~ a 4 cm. port.
Table 1. Pituitary Adenomas-Late Cerebrospinal Fluid Fistula in 9 Patients Onset of symptoms (1932 to 1967) Age at onset-28 to 54 years Sex Women-6 Men-3 3 Patients acromegalic Period from onset of symptoms to death or to 1971 Deceased-3 patients: 3, 17. 36 years Survivors-6 patients: 5, 12, 15,20,26,28 years Initial treatment of adenoma Radiation alone-3 patients Surgery and radiation-6 patients Onset of symptoms to initial treatment-l to 6 years Initial treatment of adenoma to onset of fistula 5 Patients -1 to 4 years 4 Patients-6 to 15 years Results Surgery-8 patients Successful-7 patients Required 3 operations to close fistula; died 1 year after last operation from hydrocephalus -1 patient No surgery-l patient (fistula closed after two bouts of meningitis)
CEREBROSPINAL RHINORRHEA IN PITUITARY TUMORS
285
In every instance it took at least 1 year for rhinorrhea to develop, and in 4 patients it did not develop until 6 to 15 years after initial treatment (Table 1). Although these tumors were all large initially, it was found, during a subsequent operation to close the fistula, that little or no active tumor and sometimes only a small amount of necrotic adenomatous tissue was present. The growth patterns of these tumors included temporal extensions and ocular nerve involvement in a few cases, always the third and sixth nerves. In 6 of the 9 patients compression of the optic nerves, chiasm, or tract was present. Meningitis was common among the group, and 1 patient had pneumocephalus with ventriculitis. During the early part of this series 6 of the patients were under the care of Horrax and Poppen of our clinic. Poppen!; has previously stressed the importance of closing the sphenoid sinus in such cases. The operative technique begins with exposure of the planum sphenoidale through a right frontal approach, retracting the right frontal lobe, affording the opportunity to explore the optic nerves, chiasm, and also the cribriform and ethmoid areas to be certain no opening is present. In all of these patients the fistula was obviously in the sphenoid sinus. Once the dura over the planum and anterior to the tuberculum is incised and separated from underlying bone, the tuberculum sellae is then excised and a generous bony window is developed in the anterior roof of the sphenoid sinus, carrying this opening well across the midline on each side. At this point the procedure is quite similar to that described for hypophysectomy2 in cases of a prefixed optic chiasm and posterior extending tuberculum. Some of the mucosa from the sphenoid sinus can usually be dissected free and displaced anteriorly and inferiorly. Once the upper part of the tuberculum has been taken away and the sphenoid area opened in cases where an eroding tumor is present little additional bone is left to be removed. The sella has usually been eroded or destroyed by the tumor and a large area of cavitation is then found, readily communicating with the chiasmatic cistern, sometimes with a small amount of residual adenoma or necrotic debris (Fig. 1).
Figure 1. A, Pituitary adenoma eroding sphenoid sinus. B, Large cavity remains after excision and radiation. Spinal fluid may also come through opening in thinned-out dorsum. C. Method of packing with muscle and Surgicei to close fistula from above.
286
CHARLES
A.
FAGER
When the necrotic tissue or residual tumor has been removed and a thorough debridement has been accomplished, using a lighted retractor, it is usually possible to visualize the dorsum sellae that also has been markedly thinned out by tumor and sometimes is the site of a secondary fistulous communication with the prepontine or interpeduncular cistern. Throughout the dissection, the sphenoid sinus mucosa is displaced downward and forward toward the nasopharynx so that the entire area can then be packed with a graft of muscle and Surgicel (Fig. 1). This type of operative approach has been uniformly successful (Table 1). One patient was considered a poor result because repeated operations were required. Subsequently, hydrocephalus developed, although the fistula remained closed. The patient's condition was never satisfactory, and death occurred as a result of hydrocephalus that, in our present state of knowledge, might well have been prevented by a ventricular shunting procedure. The other 7 patients who underwent operation have had successful results, and in 1 patient, no surgery was necessary because the fistula closed after a second attack of meningitis. The three case summaries reported here are representative of the group. Rhinorrhea developed 10 years after treatment in one of the three, a 41 year old man whose acromegaly was controlled by radiation therapy. The initial skull roentgenogram is characteristic (Fig. 2) and quite similar in appearance to all of the other cases. The other two patients summarized are women who had large temporal extensions into the middle fossa, both of whom underwent surgical excision of the tumor in addition to radiation therapy, and rhinorrhea subsequently developed (Figs. 3, 4, and 5).
Figure 2 (Case 1). Lateral roentgenogram showing pituitary adenoma eroding floor of sella into sphenoid region.
CEREBROSPINAL RHINORRHEA IN PITUITARY TUMORS
287
Figure 3 (Case 3). A. Right carotid arteriogram (lateral view) showing displacement of Sylvian vessels by temporal extension of pituitary adenoma. B. Same view 6 months after surgical excision and radiation. Vessels restored to normal position.
288
Figure 4 (Case 3).
CHARLES
A.
FAGER
Anteroposterior view. A, Preoperative, and B, 6 months postoperative.
Figure 5 (Case 3). Lateral roentgenogram following surgical repair of fistula. Clips placed on muscle pack in region of sphenoid sinus to demonstrate area of packing.
CEREBROSPINAL RHINORRHEA IN PITUITARY TUMORS
289
REPORTS OF CASES
CASE 1. In 1949 a 41 year old man experienced the onset of acromegaly. The patient complained of progressive facial changes and headache. He was treated for diabetes with 25 units of insulin a day. At this time no visual signs were present. In 1955, at the age of 47, the patient received 4000 R of 2 Mev radiation therapy. In 1956 he was well with no headache, and the administration of insulin had been discontinued. From 1957 to 1960 the patient was seen annually and remained well. In 1960 no evidence of active acromegaly was noted, and soft tissue regression was observed. Five years later the patient experienced the onset of rhinorrhea. A craniotomy was performed, a small amount of tumor (chromophobe) was removed, and the fistula was closed. In 1972 the patient remains well at the age of 64. CASE 2. A 26 year old woman experienced the onset of headache, amenorrhea, and diplopia in 1956. In 1958, left third and sixth nerve paresis was noted. A large, left temporal adenoma was discovered. Excision to the cavernous sinus was performed by way of a temporal craniotomy. The patient received 5000 R of 2 Mev radiation therapy after operation. Recovery was good, and in 1957 the patient had no headaches and third and sixth nerve function was normal. From 1960 to 1965 the patient was well and taking cortisone and thyroid. In November 1965 she experienced recurrent headaches, mental change was progressive, and she was incontinent. Spontaneous pneumocephalus was noted on roentgenography. In January 1966 a left frontal craniotomy was performed that revealed a small fragment of necrotic adenoma and a fistula through the clivus. The patient recovered fully from the operation and was well at the age of 42 in 1972. CASE 3. This 42 year old woman had never menstruated. In 1967 she complained of progressive fatigue. Left inferior homonymous quadrantanopia and an enlarged sella were noted. Pneumoencephalography revealed suprasellar extension. The patient received 5000 R of radiation therapy. In 1969 left hemiparesis and right sixth nerve paresis and a questionable right fifth nerve paresis were noted. The left homonymous defect appeared to be the same as seen in 1967. Arteriography showed a massive right temporal extension. A right temporal craniotomy was performed, and a large tumor compressing the optic tract, cerebral peduncle, and the fifth nerve was removed. The patient recovered but no change was observed in the visual fields and corneal sensation was impaired. Through right frontal craniotomy the small sellar and suprasellar portion of tumor was removed. In 1971 rhinorrhea was observed. Frontal craniotomy was performed to close the fistula, and no tumor was found.
SUMMARY Untreated pituitary adenomas seldom produce cerebrospinal fluid rhinorrhea because the expanding tumor acts as a "stopper." Rhinorrhea developing immediately after trans-sphenoidal procedures and sometimes after intracranial operation was a well known complication in the past, but the more common and persistent sphenoid sinus fistula usually develops as a later sequel of radiation therapy or surgery. In a series of more than 400 pituitary tumors at the Lahey Clinic, this type of late complication has been encountered in 9 patients. All had undergone previous radiation therapy or surgery, or both. In each instance the rhinorrhea was persistent and severe, and pneumocephalus and ven-
290
CHARLES
A.
FAGER
triculitis also developed in 1 patient. The tumors were all large chromophobe adenomas. Three patients had acromegaly; of particular interest is the fact that in each instance little or no active tumor was present in the sphenoid sinus when repair was carried out. Surgical procedures to close the sphenoid sinus from above have uniformly been successful in correcting this problem.
REFERENCES l. Campbell, R.L., Zeman, W., and Joyner, J.: Spontaneous rhinorrhea due to pituicytoma.
Case report. J. Neurosurg. 25:208-210 (Aug.) 1966. 2. Fager, C.A.: Pituitary ablation-current surgical techniques. Lahey Clin. Found. Bull. 18:155-163 (Oct.-Dec.) 1969. 3. Henderson, W.R.: The pituitary adenomata. A follow-up study of the surgical results in 338 cases. Brit. J. Surg. 26:811-921 (April) 1939. 4. Kay, S., Lees, J.K., and Stout, A.P.: Pituitary chromophobe tumors of the nasal cavity. Cancer 3:695-704 (July) 1950. 5. Norsa, L.: Cerebrospinal rhinorrhea with pituitary tumors. Neurology 3:864-868 (Nov.) 1953. 6. Poppen, J.L.: An Atlas of Neurosurgical Techniques. Philadelphia, W.E. Saunders Company, 1960. 522 pp. 7. Ray, B.S., and Bergland, R.M.: Cerebrospinal fluid fistula: clinical aspects, techniques of localization, and methods of closure. J. Neurosurg. 30:399-405 (April) 1969. 8. Shea, J.J.: Cerebrospinal rhinorrhea with autopsy report. Ann. Otol. Rhinol. Laryngol. 47:253-260 (March) 1938. Lahey Clinic Foundation 605 Commonwealth Avenue Boston, Massachusetts 02215
Nature and Treatment of Cerebrospinal Fluid Rhinorrhea in Pituitary Tumors
Charles A. Fager, M.D.
Untreated pituitary adenomas seldom produce cerebrospinal fluid rhinorrhea, because the expanding tumor acts as a "stopper." In a search of the literature, only seven proved pituitary neoplasms were found in which cerebrospinal fluid drainage was spontaneous.!, 4, 5, R Other isolated cases have been reported, all following treatment of the tumor either immediately after operation or as a later sequel of radiation or surgery. Ray and Berglund,7 in their paper on rhinorrhea, gave examples of both. Henderson,3 who reported Cushing's series of 338 cases, found 8 patients with a downward extension of the tumor that was so large it actually presented in the nasopharynx. None of these patients had rhinorrhea, and, interestingly enough, no leaks occurred after operation. On reviewing these cases it seems clear that only a small portion of the adenoma was removed, probably because of the dreaded threat of meningitis, so that the large bulk of the tumor still acted as a barrier even though the chiasmal reservoir was opened. This seems to be the important mechanism preventing spontaneous rhinorrhea. Cerebrospinal fluid leakage has always been a well recognized, immediate complication of pituitary surgery especially by previous transsphenoidal types of operations but, in our series at the Lahey Clinic Foundation, the major and persistent instances of rhinorrhea have all occurred as a later complication of treatment. In this regard two factors seem significant. First is our traditional reluctance to perform trans-sphenoidal operations and second is our long-standing interest in radiation therapy, which has successfully been employed for these lesions for many years. It seems possible that necrosis in the thinned-out tumor capsule or dura may be of some importance in the later development of rhinorrhea as a result of the subsequent pulsatile fluid forces at work following treatment. In a series of more than 400 pituitary tumors, this type of late complication has been encountered in 9 patients. All these tumors exhibited some of the variables of pituitary tumors but also, in some ways, conformed to a pattern in their natural and therapeutic courses. Surgical Clinics of North America- Vol. 53, No.2, April 1973
283
284
CHARLES A. FAGER
All these patients presented with a long or moderately long history of slowly growing tumor eroding the sella for many years, not always a particularly invasive neoplasm but in every instance showing a marked downward extension by radiography, obviously involving and usually obliterating the sphenoid sinus (Table 1). Periods of observation ranged from 3 to 36 years among the patients who are deceased (Table 1). The patient who was observed for only 3 years died 6 months after surgery as a result of hydrocephalus after closure of the fistula, this being the only patient in the series in whom treatment did not lead to a successful outcome. Otherwise, this patient would also have had a much longer period of observation. The one among the survivors who has been observed for only 5 years was first seen in 1967. The other 2 patients, who are deceased, died of causes unrelated to their pituitary tumors. Autopsy was performed on the patient who survived for 36 years, and a small amount of residual adenoma was found. All the patients in this group had radiation treatment; 6 underwent surgery as well during the initial treatment of the pituitary adenoma (Table 1). Some of the earlier patients in the series received conventional radiation therapy to the region of the pituitary fossa. The patients treated since 1950 were given 2 Mev radiation therapy by a rotational method as previously described with a tumor dose of '4000 R delivered to the region of the pituitary tumor throug~ a 4 cm. port.
Table 1. Pituitary Adenomas-Late Cerebrospinal Fluid Fistula in 9 Patients Onset of symptoms (1932 to 1967) Age at onset-28 to 54 years Sex Women-6 Men-3 3 Patients acromegalic Period from onset of symptoms to death or to 1971 Deceased-3 patients: 3, 17. 36 years Survivors-6 patients: 5, 12, 15,20,26,28 years Initial treatment of adenoma Radiation alone-3 patients Surgery and radiation-6 patients Onset of symptoms to initial treatment-l to 6 years Initial treatment of adenoma to onset of fistula 5 Patients -1 to 4 years 4 Patients-6 to 15 years Results Surgery-8 patients Successful-7 patients Required 3 operations to close fistula; died 1 year after last operation from hydrocephalus -1 patient No surgery-l patient (fistula closed after two bouts of meningitis)
CEREBROSPINAL RHINORRHEA IN PITUITARY TUMORS
285
In every instance it took at least 1 year for rhinorrhea to develop, and in 4 patients it did not develop until 6 to 15 years after initial treatment (Table 1). Although these tumors were all large initially, it was found, during a subsequent operation to close the fistula, that little or no active tumor and sometimes only a small amount of necrotic adenomatous tissue was present. The growth patterns of these tumors included temporal extensions and ocular nerve involvement in a few cases, always the third and sixth nerves. In 6 of the 9 patients compression of the optic nerves, chiasm, or tract was present. Meningitis was common among the group, and 1 patient had pneumocephalus with ventriculitis. During the early part of this series 6 of the patients were under the care of Horrax and Poppen of our clinic. Poppen!; has previously stressed the importance of closing the sphenoid sinus in such cases. The operative technique begins with exposure of the planum sphenoidale through a right frontal approach, retracting the right frontal lobe, affording the opportunity to explore the optic nerves, chiasm, and also the cribriform and ethmoid areas to be certain no opening is present. In all of these patients the fistula was obviously in the sphenoid sinus. Once the dura over the planum and anterior to the tuberculum is incised and separated from underlying bone, the tuberculum sellae is then excised and a generous bony window is developed in the anterior roof of the sphenoid sinus, carrying this opening well across the midline on each side. At this point the procedure is quite similar to that described for hypophysectomy2 in cases of a prefixed optic chiasm and posterior extending tuberculum. Some of the mucosa from the sphenoid sinus can usually be dissected free and displaced anteriorly and inferiorly. Once the upper part of the tuberculum has been taken away and the sphenoid area opened in cases where an eroding tumor is present little additional bone is left to be removed. The sella has usually been eroded or destroyed by the tumor and a large area of cavitation is then found, readily communicating with the chiasmatic cistern, sometimes with a small amount of residual adenoma or necrotic debris (Fig. 1).
Figure 1. A, Pituitary adenoma eroding sphenoid sinus. B, Large cavity remains after excision and radiation. Spinal fluid may also come through opening in thinned-out dorsum. C. Method of packing with muscle and Surgicei to close fistula from above.
286
CHARLES
A.
FAGER
When the necrotic tissue or residual tumor has been removed and a thorough debridement has been accomplished, using a lighted retractor, it is usually possible to visualize the dorsum sellae that also has been markedly thinned out by tumor and sometimes is the site of a secondary fistulous communication with the prepontine or interpeduncular cistern. Throughout the dissection, the sphenoid sinus mucosa is displaced downward and forward toward the nasopharynx so that the entire area can then be packed with a graft of muscle and Surgicel (Fig. 1). This type of operative approach has been uniformly successful (Table 1). One patient was considered a poor result because repeated operations were required. Subsequently, hydrocephalus developed, although the fistula remained closed. The patient's condition was never satisfactory, and death occurred as a result of hydrocephalus that, in our present state of knowledge, might well have been prevented by a ventricular shunting procedure. The other 7 patients who underwent operation have had successful results, and in 1 patient, no surgery was necessary because the fistula closed after a second attack of meningitis. The three case summaries reported here are representative of the group. Rhinorrhea developed 10 years after treatment in one of the three, a 41 year old man whose acromegaly was controlled by radiation therapy. The initial skull roentgenogram is characteristic (Fig. 2) and quite similar in appearance to all of the other cases. The other two patients summarized are women who had large temporal extensions into the middle fossa, both of whom underwent surgical excision of the tumor in addition to radiation therapy, and rhinorrhea subsequently developed (Figs. 3, 4, and 5).
Figure 2 (Case 1). Lateral roentgenogram showing pituitary adenoma eroding floor of sella into sphenoid region.
CEREBROSPINAL RHINORRHEA IN PITUITARY TUMORS
287
Figure 3 (Case 3). A. Right carotid arteriogram (lateral view) showing displacement of Sylvian vessels by temporal extension of pituitary adenoma. B. Same view 6 months after surgical excision and radiation. Vessels restored to normal position.
288
Figure 4 (Case 3).
CHARLES
A.
FAGER
Anteroposterior view. A, Preoperative, and B, 6 months postoperative.
Figure 5 (Case 3). Lateral roentgenogram following surgical repair of fistula. Clips placed on muscle pack in region of sphenoid sinus to demonstrate area of packing.
CEREBROSPINAL RHINORRHEA IN PITUITARY TUMORS
289
REPORTS OF CASES
CASE 1. In 1949 a 41 year old man experienced the onset of acromegaly. The patient complained of progressive facial changes and headache. He was treated for diabetes with 25 units of insulin a day. At this time no visual signs were present. In 1955, at the age of 47, the patient received 4000 R of 2 Mev radiation therapy. In 1956 he was well with no headache, and the administration of insulin had been discontinued. From 1957 to 1960 the patient was seen annually and remained well. In 1960 no evidence of active acromegaly was noted, and soft tissue regression was observed. Five years later the patient experienced the onset of rhinorrhea. A craniotomy was performed, a small amount of tumor (chromophobe) was removed, and the fistula was closed. In 1972 the patient remains well at the age of 64. CASE 2. A 26 year old woman experienced the onset of headache, amenorrhea, and diplopia in 1956. In 1958, left third and sixth nerve paresis was noted. A large, left temporal adenoma was discovered. Excision to the cavernous sinus was performed by way of a temporal craniotomy. The patient received 5000 R of 2 Mev radiation therapy after operation. Recovery was good, and in 1957 the patient had no headaches and third and sixth nerve function was normal. From 1960 to 1965 the patient was well and taking cortisone and thyroid. In November 1965 she experienced recurrent headaches, mental change was progressive, and she was incontinent. Spontaneous pneumocephalus was noted on roentgenography. In January 1966 a left frontal craniotomy was performed that revealed a small fragment of necrotic adenoma and a fistula through the clivus. The patient recovered fully from the operation and was well at the age of 42 in 1972. CASE 3. This 42 year old woman had never menstruated. In 1967 she complained of progressive fatigue. Left inferior homonymous quadrantanopia and an enlarged sella were noted. Pneumoencephalography revealed suprasellar extension. The patient received 5000 R of radiation therapy. In 1969 left hemiparesis and right sixth nerve paresis and a questionable right fifth nerve paresis were noted. The left homonymous defect appeared to be the same as seen in 1967. Arteriography showed a massive right temporal extension. A right temporal craniotomy was performed, and a large tumor compressing the optic tract, cerebral peduncle, and the fifth nerve was removed. The patient recovered but no change was observed in the visual fields and corneal sensation was impaired. Through right frontal craniotomy the small sellar and suprasellar portion of tumor was removed. In 1971 rhinorrhea was observed. Frontal craniotomy was performed to close the fistula, and no tumor was found.
SUMMARY Untreated pituitary adenomas seldom produce cerebrospinal fluid rhinorrhea because the expanding tumor acts as a "stopper." Rhinorrhea developing immediately after trans-sphenoidal procedures and sometimes after intracranial operation was a well known complication in the past, but the more common and persistent sphenoid sinus fistula usually develops as a later sequel of radiation therapy or surgery. In a series of more than 400 pituitary tumors at the Lahey Clinic, this type of late complication has been encountered in 9 patients. All had undergone previous radiation therapy or surgery, or both. In each instance the rhinorrhea was persistent and severe, and pneumocephalus and ven-
290
CHARLES
A.
FAGER
triculitis also developed in 1 patient. The tumors were all large chromophobe adenomas. Three patients had acromegaly; of particular interest is the fact that in each instance little or no active tumor was present in the sphenoid sinus when repair was carried out. Surgical procedures to close the sphenoid sinus from above have uniformly been successful in correcting this problem.
REFERENCES l. Campbell, R.L., Zeman, W., and Joyner, J.: Spontaneous rhinorrhea due to pituicytoma.
Case report. J. Neurosurg. 25:208-210 (Aug.) 1966. 2. Fager, C.A.: Pituitary ablation-current surgical techniques. Lahey Clin. Found. Bull. 18:155-163 (Oct.-Dec.) 1969. 3. Henderson, W.R.: The pituitary adenomata. A follow-up study of the surgical results in 338 cases. Brit. J. Surg. 26:811-921 (April) 1939. 4. Kay, S., Lees, J.K., and Stout, A.P.: Pituitary chromophobe tumors of the nasal cavity. Cancer 3:695-704 (July) 1950. 5. Norsa, L.: Cerebrospinal rhinorrhea with pituitary tumors. Neurology 3:864-868 (Nov.) 1953. 6. Poppen, J.L.: An Atlas of Neurosurgical Techniques. Philadelphia, W.E. Saunders Company, 1960. 522 pp. 7. Ray, B.S., and Bergland, R.M.: Cerebrospinal fluid fistula: clinical aspects, techniques of localization, and methods of closure. J. Neurosurg. 30:399-405 (April) 1969. 8. Shea, J.J.: Cerebrospinal rhinorrhea with autopsy report. Ann. Otol. Rhinol. Laryngol. 47:253-260 (March) 1938. Lahey Clinic Foundation 605 Commonwealth Avenue Boston, Massachusetts 02215