Parasellar Extension Research Articles

Paraganglioma in pituitary fossa

Paragangliomas are neuroendocrine tumors of paraganglionic tissue which are extremely rare in the sellar area. We present a case of sellar paraganglioma with parasellar and suprasellar extension in a 70-year-old man who presented with headache. CT demonstrated sellar mass with suprasellar and right parasellar extension. The lesion was removed subtotally via a trans-sphenoidal approach. Histopathological diagnosis was paraganglioma. Differential diagnosis between paragangliomas and unusual types of pituitary adenomas, especially null-cell adenomas, is made by presence of cell nests (Zellballen) in paraganglioma, lack of immunopositivity for pituitary hormones, cytoplasmic immunopositivity for chromogranin A and neuron-specific enolase, and immunonegativity for cytokeratin 19, cytokeratin 20 and endomysial antibody. In the case of a mass in the sellar region, paraganglioma, although rare, should be included in the differential diagnosis.

PURE ENDOSCOPIC ENDONASAL APPROACH FOR PITUITARY ADENOMAS

The aim of this study was to report the results of a consecutive series of patients undergoing pituitary surgery using a pure endoscopic endonasal approach and to evaluate the efficacy and safety of this procedure. We reviewed 200 consecutive patients with pituitary adenoma who underwent purely endoscopic transsphenoidal resection of their lesions. The patients' clinical outcomes, including remission rates, degrees of tumor removal, and complications, were evaluated and compared with a previous microscopic series. There were 111 nonfunctioning adenomas and 34 growth hormone-secreting, 27 adrenocorticotropin hormone-secreting, 25 prolactin-secreting, and 3 thyroid-stimulating hormone-secreting adenomas. The degree of gross total removal for tumors with suprasellar or parasellar extension and without cavernous sinus involvement was 96% and for intrasellar lesions was 98%. After a median follow-up period of 19 months, the remission results for patients with functioning adenomas were 71% for growth hormone-secreting, 81% for adrenocorticotropin hormone-secreting, and 88% for prolactin-secreting adenomas, with no recurrence at the time of the last follow-up. This compares with similar results reported from series using a standard microsurgical approach (growth hormone-secreting adenomas, 67%; adrenocorticotropin hormone-secreting adenomas, 78%; and prolactin-secreting adenomas, 62%). Endoscopic surgery for recurrent or residual nonfunctioning adenomas that had been previously treated using a microscopic approach revealed in the majority of cases a more limited exposure during the initial surgery, frequently with incomplete tumor removal. Complication rates have been low, and the average length of hospital stay was reduced. A purely endoscopic approach for pituitary adenoma treatment is a safe and effective alternative to the traditional microscopic procedure. Although our results reveal excellent tumor-removal rates, comparable remission rates in functioning tumors, and a very low rate of complications, additional studies with longer follow-up periods are required to confirm whether this approach should be considered the preferred procedure for pituitary surgery.

TUBERCULUM SELLAE MENINGIOMAS

Tuberculum sellae meningiomas represent 5 to 10% of all intracranial meningiomas. Such lesions are classically removed through a variety of well-standardized transcranial approaches. The extended endonasal transsphenoidal route, under either microscopic or endoscopic visualization, has only recently been proposed as a viable surgical technique for the management of such tumors. A total of 51 consecutive patients with tuberculum sellae meningiomas were treated at our institution during a 21-year period. Forty-four patients had transcranial surgery, and the last seven were treated via the extended endoscopic transsphenoidal approach. We also compared our data with those reported in the pertinent literature related to the surgical, ophthalmological, and endocrinological outcome. The significant difference among the transcranial and transsphenoidal series, both in our experience and in the reviewed literature, did not allow us to draw statistically significant results but rather a reporting of the outcomes. In the transcranial group, 86.4% had a gross total removal of the lesion, whereas the percentage was 83.3% in the transsphenoidal group. Concerning the visual outcome, we experienced postoperative improvement in 61.4% of the transcranial patients and a worsening of 13.6%, whereas improvement was reported in 71.4% of the patients in the transsphenoidal group; in the last group, we did not observe any postoperative worsening. The main drawback of the transsphenoidal approach still remains the difficulty in reconstructing the cranial base dural and bone defects, which expose patients to a greater risk of postoperative cerebrospinal fluid leakage (28.6% in our series) and related complications. When treating a patient with a diagnosis of tuberculum sellae meningioma, a neurosurgeon should know that, aside from the classical transcranial approach, the possibility of an extended transsphenoidal approach exists. Although it is still not a standardized procedure, in carefully selected cases (i.e., small midline lesions, without major vessel encasement, or parasellar extension) and in experienced hands, it could be considered a viable alternative, especially in overcoming the reconstruction-related problems.

Comparison of lateral and superior walls of the pituitary fossa with clinical emphasis on pituitary adenoma extension: cadaveric-anatomic study

Pituitary adenomas extend to the suprasellar region via diaphragmal passage and extend to the cavernous sinus via the medial wall (MW). Better understanding of the dynamics of suprasellar and parasellar extension of sellar region pathologies requires microanatomical comparison of diaphragma sellae (DS) and the MW of the cavernous sinus. This study provides the first detailed quantitative assessment between DS and MW of the cavernous sinus. Microanatomical details and histopathological examinations of the DS and MWs of the cavernous sinus were studied in sphenoid block samples obtained from adult cadavers, and the thicknesses of the DS and the MW of the cavernous sinus were measured. Mean thickness of the DS was 216.73 +/- 51.26 microm in the center and 367.33+/-133.66 microm in the periphery. Mean thickness of the lower third of the MW was 161.53+/-53.86 microm and that of the upper third was 278.46+/-162.79 microm. Difference between the thicknesses of the upper and lower thirds was significant (P<0.001). When the central thickness of the DS and lower third of the MW were compared, a significant difference was found (P<0.01). Our measurements suggest that when the DS is thick and the stalk opening is complete, the thickness of the lower third of the medial wall could be the major determinant of parasellar extension.

Fully Endoscopic Transsphenoidal Resection of Pituitary Tumors: Technique and Results

The aim of this study was to describe our two-surgeon fully endoscopic approach to pituitary surgery and to report results in terms of tumor remission, improvement in vision, and complications. A retrospective chart review was performed. Our prospectively recorded surgical database was searched for all endoscopic transsphenoidal procedures between January 2001 and December 2005. Those patients who had surgery had their medical charts reviewed and presenting symptoms and signs, lesion characteristics, endocrine investigations, operative details, complications, and treatment outcomes recorded. Thirty-two patients were included in the study. Twenty-three patients had macroadenomas, five patients had microadenomas, and four patients had other pathologies. Most patients with macroadenomas had significant supra- or parasellar extension. Of the 14 patients who had visual loss at presentation, 13 had postoperative improvement. Two patients had postoperative cerebrospinal fluid leaks, which were successfully treated endoscopically. Eight patients required some form of hormone replacement after surgery. After a mean follow-up of 31 months, the overall remission rate for patients with macroadenomas was 82% and for patients with microadenomas was 100%. The fully endoscopic transsphenoidal approach provides excellent visualization for tumor resection and results in acceptable remission rates.

Rupture of a craniopharyngioma cyst following trauma: a case report

There have been only 20 reported cases of non-surgical rupture of a craniopharyngioma cyst, with only 3 cases secondary to trauma. Here we present a rare case of temporary shrinkage of a cystic craniopharyngioma following head trauma. After a motor vehicle accident in May 2001, a 61-year old woman began to have blurred vision and headaches. Magnetic resonance imaging (MRI) of the head revealed a primarily cystic mass measuring approximately two centimeters, involving the sellar and suprasellar area with compression of the pituitary. Visual field testing showed a left hemianopsia and the patient was referred for surgical evaluation. Transsphenoidal drainage of the cystic lesion in November 2001 provided histologic confirmation of the craniopharyngioma. Post-operative MRI showed cyst reduction and visual fields improved. Late in 2002, the patient again experienced progressive visual loss. Repeat MRI revealed a recurrent cystic craniopharyngioma, now measuring approximately three centimeters with subfrontal and parasellar extension and compression of the optic chiasm. A bifrontal surgical approach was advocated; however, prior to the scheduled surgery, the patient sustained a fall with trauma to the head. Following this event she experienced dramatic improvement in her headache and vision and repeat MRI showed the cystic lesion to be significantly decreased in size. Spontaneous rupture of craniopharyngioma cysts is uncommon but has been reported with increasing frequency. It is, however, exceedingly rare for a cyst to rupture following trauma.

EXTENDED ENDOSCOPIC ENDONASAL TRANSSPHENOIDAL APPROACH FOR THE REMOVALOF SUPRASELLAR TUMORS

The widespread use of the endoscope in transsphenoidal pituitary surgery has recently contributed to the extension of the approach beyond the tuberculum sellae and planum sphenoidale for the management of lesions located in the suprasellar area, either with an endoscope-assisted or purely endoscopic technique. Based on our previous experience with more than 450 standard endoscopic transsphenoidal operations, we have retrospectively evaluated the effectiveness of the extended endoscopic endonasal transsphenoidal approach in the management of lesions mainly located in the suprasellar area. Between January 2004 and December 2005, 20 consecutive patients underwent extended endoscopic endonasal transsphenoidal surgery for a total of 21 procedures. The series consisted of seven pituitary adenomas, seven craniopharyngiomas, three suprasellar Rathke's cleft cysts, two tuberculum sellae meningiomas, and one pilocytic astrocytoma of the chiasm. Tumor removal, as assessed by postoperative magnetic resonance imaging, revealed complete removal of the lesion in four out of seven pituitary adenomas, five out of seven craniopharyngiomas, three out of three Rathke's cleft cysts, and two out of two tuberculum sellae meningiomas. One patient (5%) with craniopharyngioma had a postoperative cerebrospinal fluid leak that required reoperation. The same patient experienced a sphenoid mycosis, which was treated with medical therapy. Some specific conditions associated with the anatomy of the surgical route, as well as to the morphology of the lesion, have resulted to condition the feasibility of the approach. Small and medium sized suprasellar lesions located in the midline, with or without a limited parasellar extension and without involvement of vascular structures, seem amenable to be resected through such extended endoscopic transsphenoidal approach. Improvements in closure techniques and the use of new materials and surgical glues seem to significantly reduce the postoperative cerebrospinal fluid leak rate and meningitis.

Influence of parasellar extension of macroprolactinomas defined by magnetic resonance imaging on their responsiveness to dopamine agonist therapy

Influence of parasellar extension of macroprolactinomas defined by magnetic resonance imaging on their responsiveness to dopamine agonist therapy

Influence of parasellar extension of macroprolactinomas defined by magnetic resonance imaging on their responsiveness to dopamine agonist therapy

The resistance of macroprolactinomas to dopamine agonist (DA) therapy, whether defined as an absence of PRL normalization or the lack of significant tumour shrinkage after prolonged treatment at high doses, is usually regarded as unpredictable. The aim of this retrospective study, conducted in a teaching hospital, was to determine whether cavernous sinus (CS) invasion assessed by magnetic resonance imaging (MRI) is associated with a higher rate of resistance to DA therapy. Forty-nine patients with a macroprolactinoma were included in this study and classified into four groups according to the percentage of encasement of the intracavernous internal carotid artery (ICA) by the tumour. All patients received DA as the primary treatment, mainly cabergoline (CAB). PRL normalization and tumour shrinkage during treatment were evaluated as a function of CS invasion. Tumours encasing more than three-quarters of the intracavernous ICA (group 4) were less responsive to DA therapy, exhibiting a lower rate of early (< or = 3 months) PRL normalization (8%vs. 69% in the others groups; P < 0.01) under a higher dose of CAB (median: 3.5 mg vs. 1.0 mg per week; P < 0.01). CS invasion was a strongly significant and independent predictor of hormonal resistance to CAB (P < 0.01). This hormonal resistance occurred in eight patients (16%), all but one belonging to group 4. Significant tumour shrinkage was observed in 31 out of 45 assessable cases (69%) and was more likely to occur in the case of PRL normalization (P < 0.01). Parasellar extension of macroprolactinomas, assessed on the basis of strict MRI criteria, may predict a negative response to DA. The responsiveness of noninvasive macroprolactinomas (over 90%) is similar to that reported in microprolactinomas, whereas invasive tumours are resistant to treatment in more than 50% of cases.

Evaluation of magnetic resonance imaging criteria for cavernous sinus invasion in patients with pituitary adenomas: logistic regression analysis and correlation with surgical findings

Background This study used high-resolution magnetic resonance (MR) imaging (1.5 T) to define and evaluate preoperative imaging criteria for cavernous sinus invasion (CSI) by pituitary adenoma (PA). Methods Magnetic resonance images obtained from 103 patients with PA submitted to surgery (48 with CSI) were retrospectively reviewed. The following MR signs were studied and compared with intraoperative findings: (1) presence of normal pituitary gland between the adenoma and cavernous sinus (CS), (2) status of the CS venous compartments, (3) CS size, (4) CS lateral wall bulging, (5) displacement of the intracavernous internal carotid artery (ICA) by adenoma, (6) grade of parasellar extension (Knosp-Steiner classification 1), and (7) percentage of intracavernous ICA encased by the tumor. Statistical analysis was performed using χ 2 testing, and sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were obtained for each MR finding. The odds ratio of the most significant criteria was also obtained, and the multiple logistic regression test was used to compare the criteria altogether. Results The following signs have been found to represent accurate criteria for noninvasion of the CS: (1) normal pituitary gland interposed between the adenoma and the CS (PPV, 100.0%), (2) intact medial venous compartment (PPV, 100.0%), and (3) percentage of encasement of the intracavernous ICA lower than 25% (NPV, 100.0%). Cavernous sinus invasion was certain if the percentage of encasement of the intracavernous ICA was higher than 45% and 3 or more CS venous compartments were not depicted. The most valuable criterion of CSI by logistic regression analysis was the percentage of encasement of intracavernous ICA of 30% or more, with an odds ratio of 49.25. Conclusion The preoperative diagnosis of CSI by PA is extremely important because endocrinologic remission is rarely obtained after microsurgery alone in patients with invasive tumors. The aforementioned MR imaging criteria may be useful in patient's management and in advising most of the patients preoperatively on the potential need for complimentary therapy after surgery.

Magnetic resonance imaging and biological markers in pituitary adenomas with invasion of the cavernous sinus space

The preoperative diagnosis of cavernous sinus invasion remains difficult and controversial, and there are currently no reliable histological or molecular markers that predict pituitary tumour behaviour and response to treatment. We evaluated 45 patients with pituitary adenoma. The results have shown that the sensitivity of MRI for indicating cavernous sinus invasion in this prospective study was 60%, specificity 85%, positive predictive value 83.33%, negative predictive value 62.96%. Forty-five specimens of pituitary adenomas were analyzed for expression of F8, VEGF, Ki-67, c-myc, bcl-2, nm23 and MMP-9 immunoreactivity using immunoperoxidase staining. MVD was assessed using F8-related antigen. The results have shown that MVD of invasive pituitary adenomas was significantly higher than that of noninvasive (P < 0.001). There was an association between the invasion of pituitary adenomas and Ki-67 LI (P = 0.039) or the expression of VEGF (P < 0.001) and MMP-9 (P < 0.001). But c-myc LI and bcl-2 expression have no association with invasiveness of pituitary adenomas (P = 0.061 vs. P = 0.201). On the other hand, there is an inverse relationship between nm23 expression and tumor invasion (P < 0.001). In conclusion, parasellar extension of pituitary adenomas through the medial wall of the cavernous sinus diagnosed at surgery, can be determined by radiology with sensitive gadolinium-enhanced MRI. Although our study has shown that MVD and the expression of VEGF, Ki-67, nm23 and MMP-9 have associations with invasiveness of pituitary adenomas, they are lack of specificity. These markers can only provide some useful informations on the therapeutic strategy of pituitary adenomas.

Multilocated mature teratoma: a case report and review of the literature

Mature teratomas are rare inclusion tumors, which have benign behaviors. Different locations of the tumor were reported in the literature. However, multiple tumor locations are extremely rare. An eight year old patient presented with an intraventricularly mature teratoma. During the six year follow up-period, two separately located masses were observed in the chest area and in the right iliac region, and both tumors were histologically diagnosed as mature teratomas. In this study, this unique case of mature teratoma presented with multiple locations in three separate body compartments. Furthermore, intraventricular dissemination with sellar and parasellar extension was observed in the third ventricle.

Magnetic resonance imaging of cavernous sinus invasion by pituitary adenoma diagnostic criteria and surgical findings.

This study used MRI to define preoperative imaging criteria for cavernous sinus invasion (CSI) by pituitary adenoma (PA). MR images of 103 patients with PA submitted to surgery (48 with CSI) were retrospectively reviewed. The following MR signs were studied and compared to intraoperative findings (the latter were considered the gold standard for CSI detection): presence of normal pituitary gland between the adenoma and CS, status of the CS venous compartments, CS size, CS lateral wall bulging, displacement of the intracavernous internal carotid artery (ICA) by adenoma, grade of parasellar extension (Knosp-Steiner classification) and percentage of intracavernous ICA encased by the tumor. Statistical analysis was performed using qui-square testing and sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were obtained for each MR finding. The following signs have been found to represent accurate criteria for non-invasion of the CS: 1- normal pituitary gland interposed between the adenoma and the CS (PPV, 100%); 2- intact medial venous compartment (PPV, 100%); 3- percentage of encasement of the intracavernous ICA lower than 25% (NPV, 100%) and 4- medial intercarotid line not crossed by the tumor (NPV, 100%). Criteria for CSI were: 1- percentage of encasement of the intracavernous ICA higher than 45%; 2- occlusion of three or more CS venous compartments and 3- occlusion of the CS lateral venous compartment. The CS was very likely to be invaded if the inferior venous compartment was not detected (PPV. 92,8%), if the lateral intercarotid line was crossed (PPV. 96,1%) or if a bulging lateral dural wall of the CS was seen (PPV, 92,3%). The preoperative diagnosis of CSI by PA is extremely important since endocrinological remission is rarely obtained after microsurgery alone in patients with invasive tumors. The above mentioned MR imaging criteria may be useful in advising most of the patients preoperatively on the potential need for complimentary therapy after surgery.

Giant prolactinomas in men: efficacy of cabergoline treatment.

The term 'giant prolactinoma' can be used for tumours larger than 4 cm in diameter and/or with massive extrasellar extension. Cabergoline (CAB), a long-lasting dopamine agonist (DA), safe and well tolerated, is effective in normalizing PRL levels and inducing tumour shrinkage in micro- and macroprolactinomas. The purpose of this prospective study was to evaluate the efficacy and safety of CAB also for giant prolactinomas. Ten men with giant prolactinomas with a median age of 44.8 years were treated with CAB. Before CAB, four patients had previously undergone transsphenoidal surgery without modifying the parasellar extension of the tumour or their visual defects. Pretreatment serum prolactin (PRL) levels ranged between 1230 and 22 916 micro g/l (mean +/- SEM: 5794 +/- 1996) and tumour volume was between 21.8 and 105.5 cm3 (mean +/- SEM: 50.7 +/- 8.8). CAB was administered at an initial low dose of 0.5 mg three times a week and, in five patients who did not achieve serum PRL normalization, the dose was progressively increased up to 10.5 mg/week. The duration of treatment was 13-68 months (mean 38.9). PRL levels and pituitary target organ hormones were assayed before, after 30 days and then every 3 months after the beginning of CAB treatment. Magnetic resonance imaging (MRI) was carried out before, after 1-3 months, after 6 months and then every 10-12 months to evaluate tumour shrinkage. In every patient, a significant PRL decrease (P = 0.0086) of at least 96% of the pretreatment values occurred (from 5794 +/- 1996 to 77 +/- 38, mean +/- SEM); a persistent normalization of PRL levels was achieved in five out of 10 patients (50%) beginning from the first 3-6 months of CAB treatment (only one patient needed 12 months of therapy). A significant tumour shrinkage (P = 0.0003) was achieved after 12 months of therapy in nine out of 10 patients (90%), with a volume reduction greater than 95% in three, of 50% in four and 25% in two patients. Tumour volume decreased from 50.7 +/- 8.8 to 28.6 +/- 9.4 and then to 22.3 +/- 8.8 cm3 (mean +/- SEM) after 6 and 12 months of CAB treatment, respectively. An improvement of visual field defects (VFD) was obtained in six of the seven patients presenting visual impairment before CAB treatment. Among the eight patients presenting libido and potency (L-P) failure, five normalized their PRL levels. In two of these a complete restoration of libido and potency was observed. Three patients with secondary hypoadrenalism and a patient with secondary hypothyroidism were treated with substitutive therapy during all the study time. The drug was well tolerated by all patients and no one discontinued the therapy. These data suggest that, in giant, aggressive prolactinomas, CAB represents a first-line therapy effective in reducing PRL levels and determining tumour shrinkage.

Anterior transpetrosal approach for petroclival tumors

The petroclival or prepontine tumors originating medial to the trigeminal nerve include meningiomas, trigeminal neurinomas, laterally extended chordomas and prepontine epidermoids. They frequently show middle fossa or parasellar extension and have been one of the difficult tumors requiring a combined large craniotomy or multiple step surgery. Here, we will present a surgical method of tumor removal through a keyhole, epidurally created in a petrous apex. The technical points presented are based on my experience of 95 cases. This approach has the following advantages: (1) One-stage epidural surgery to the petroclival and dumbbell parasellar–clival lesions through a small craniotomy; (2) Minimal venous complications compared to the presigmoid approach; (3) Minimal facial and lower cranial nerves injury by jumping into the petroclival area medial to the internal auditory meatus; (4) Bloodless tumor removal being possible by detachment of the tentorial artery; (5) Hearing preservation by limited petrous resection.

Neuroendoscopic endonasal transseptal approach to the sellar region: study of 30 cases

An endoscopic endonasal transsphenoidal approach to the sella was performed in 30 patients. The use of endoscope allowed close inspection and differentiation between tumor tissue and glandular remains, resulting in micro dissection of the tumor with maximum preservation of pituitary function. The angled view of the endoscope helps gross total removal of the tumor tissue, from the supra and para sellar extension. The endonasal transseptal endoscopic approach helps from dental problems, and lowers incidence of septal perforation, synechia, and crust formation. However the endoscopic approach has drawbacks. Its decreases the depth of field, needs constant manual control of the endoscope, and requires experience with the endoscope technique.

Pituitary tumours in adolescence: clinical behaviour and neuroimaging features of seven cases

The clinicopathologic features of seven paediatric patients with pituitary adenomas (2 male, 5 female; mean age 14.3 years) were reviewed. There were three non-functioning adenomas, three prolactinomas, and one growth hormone producing adenoma. Five pat ients presented with visual field deficits, and six patients had endocrine symptoms, which included menstrual irregularities in all female patients, pubertal delay in two females, and growth delay and gigantism in one case each. On neuroimaging studies, five adenomas showed parasellar extension, while the remaining two prolactinomas were intrasellar microadenomas. While two patients with prolactinomas received good results with bromocriptine treatment alone, the remaining five patients underwent either craniotomy or transsphenoidal surgery. Postoperatively, visual disturbances improved markedly in all patients. Two patients also received replacement hormonal therapy. While six patients have been stable for 3.6 years on average, one non-functioning tumo ur recurred 2 years after the initial transcranial subtotal resection of the tumour. Although there are still many unknowns concerning the biology and optimal treatments for paediatric pituitary adenomas, many of them are assumed to be relatively rapidly growing tumours, while others merely have an earlier tumour genesis than in adults.

The role of gamma knife radiosurgery in the management of pituitary adenomas.

No treatment modality has been entirely successful in the management of pituitary adenomas. Although most patients with pituitary microadenomas can be cured by transsphenoidal surgery, the results are less satisfactory in macroadenomas in particular with suprasellar and/or parasellar extension. Additional treatment is then called for. Conventional fractional radiotherapy can often control tumour growth but is limited to 45-50 Gy with a very slow reduction in elevated pituitary hormones and a high incidence of pituitary insufficiency. Stereotactic radiosurgery allows the delivery of radiation with high precision to the target with low doses to the surrounding tissues permitting higher radiation doses. Gamma knife radiosurgery using photon energy with gamma beams from multiple cobalt 60 radiation sources is now used in many centers. It can be carried out in an outpatient setting with one single treatment. A more rapid normalization of pituitary hormone hypersecretion than with conventional radiation can be achieved as well as arrest of tumour growth and reduction of tumour mass. We therefore consider gamma knife radiosurgery as a valuable compliment to pituitary surgery. Long-term prospective studies are needed to evaluate the frequency of pituitary insufficiency in patients where the target area is determined with stereotactic magnetic resonance imaging (MRI).

Pituitary adenomas in acromegaly: Comparison of different adenoma types with clinical data.

Adenoma tissues from 309 patients with active acromegaly was examined by routine light microscopy and immunohistochemistry, and selectively by electron microscopy. All adenomas were immunoreactive for growth hormone. Eighty-seven adenomas were monohormonal (28%), 58 were bihormonal (immunoreactive for growth hormone and prolactin) (19%), and 157 adenomas were plurihormonal (51%), with positivity for glyco-proteins and/or their α-subunit as well. The mean tumor size was significantly greater in monohormonal adenomas than in other adenoma types. There was no difference in invasiveness among the various adenoma types. Younger patients showed invasive tumor growth more often. Patients with densely granulated GH cell adenomas had a significantly longer duration of symptoms compared to patients with other adenoma types. More than half of the patients with sparsely granulated GH cell adenomas had a duration of less than 5 yr. There was no correlation between duration of symptoms and tumor size. The preoperative mean GH level was significantly higher in patients with sparsely granulated GH cell adenomas than in those with mixed GH/PRL cell adenomas. The preoperative mean PRL level was significantly higher in patients with bihormonal adenomas than in those with plurihormonal adenomas. There was an inverse correlation between age and preoperative GH and PRL levels. No linear correlation was found between preoperative basal GH and PRL levels. Monohormonal adenomas presented more often with suprasellar and/or parasellar extension than other adenoma types. Our data suggest a positive correlation between tumor extension and preoperative GH and PRL levels. Patients with plurihormonal adenomas were significantly older than patients with sparsely granulated GH cell adenomas and mixed GH/PRL cell adenomas. No significant difference was found between the various adenoma types and the extent of surgical removal, which depends on the degree of invasiveness, tumor size, and extrasellar tumor extension.

Clinically nonsecreting pituitary adenomas in childhood and adolescence.

Clinically nonsecreting pituitary adenomas are rare in childhood and adolescence. We analyzed five cases of clinically nonsecreting pituitary adenomas in patients (4 male and 1 female patient) under 20 years of age at surgery (0.22%), identified by a review of 2288 patients with pituitary adenomas treated from 1970 to 1996 at the Hamburg University. Patient age at the onset of symptoms ranged from 8 to 13 years (mean, 10.8 yr), and age at surgery ranged from 12.5 to 19.5 years (mean, 15.5 yr). Two patients presented with endocrine symptoms, two with headache only, and one with a visual field defect. Endocrinological examinations showed pituitary insufficiency in two patients with endocrine symptoms. The serum prolactin level was normal in all patients. Radiological investigations demonstrated resectable macroadenomas with ring enhancement in four patients and a nonresectable macroadenoma with parasellar extension in one. Transnasal explorations achieved radical tumor resection except in one patient. The latter underwent a transcranial resection and radiotherapy because of parasellar tumor rest. Surgical morbidity consisted of left oculomotor nerve palsy after transcranial exploration. In two patients, normal pituitary function was preserved by transnasal surgery. Follow-up duration was 2 to 23 years (mean, 10.9 yr). There was no recurrence except for one parasellar adenoma. Immunohistological diagnosis was null cell adenoma in two patients, silent prolactinoma in two, and silent gonadotroph adenoma in one. The proliferative activity measured by Ki-67 (as the antibody MIB-1) and p53 expression revealed a positive reaction in one adenoma with parasellar extension. Clinically nonsecreting pituitary adenomas in childhood and adolescence cause different endocrine symptoms from those in adults. They caused pubertal and growth delay and/or primary amenorrhea in the patients investigated in this study. Transnasal surgery in childhood and adolescence is as safe as in adults. The characteristics of nonsecreting pituitary adenomas in this age group, including 20 patients cited from the literature, do not differ from those in adults.