Giant pituitary neuroendocrine tumor case series

Forty patients with giant pituitary neuroendocrine tumor (24 men, age 54.2 ± 16.2 years) were studied. The maximum tumor diameter [median (interquartile range)] was 4.6 cm (4.1-5.1). Women had larger tumors [4.8 cm (4.2-5.4) vs. 4.5 cm (4.0-4.9); p=0.048]. Hypopituitarism [partial (n=22, 55%) or complete (n=9, 22.5%)] at diagnosis was present in 77.5% of the patients. Visual field defects were found in 90.9%. The most used surgical technique was endoscopic endonasal transsphenoidal (EET) surgery (n=31, 77.5%). Radiotherapy was used in 11 (27.5%) patients (median dose 50.4 Gy, range 50-54). Thirty-seven patients were followed for 36 months (10-67 months). Although more than half of these patients showed tumor persistence (n=25, 67.6%), tumor size was significantly reduced [0.8 cm (0-2.5); p<0.001]. At last visit, 12 patients (32.4%) showed absence of tumor on MRI. Hypopituitarism rate was similar (75.0%), although with significant changes (p<0.001) in the distribution of the type of hypopituitarism. The absence of a tumor at the last visit was positively associated with positive immunohistochemical staining for FSH (p=0.01) and LH (p=0.006) and negatively with female sex (p=0.011), cavernous sinus invasion (p=0.005) and the presence of Knosp grade 4 (p=0.013).

gNFPAs are more frequent in men but tumors are larger in women. Surgical treatment is followed by a complete tumor resection rate of approximately 30%. Positive immunostaining for gonadotropins is associated with tumor absence at last revision, while female sex and invasion of the cavernous sinuses with tumor persistence ¹⁾.

A retrospective study of electively operated cases of PA over a six year period was performed. Surgical outcomes and complications of 64 patients with large PAs (≥3cm) and 59 patients with giant PAs (>4cm), who underwent MTS at same period, were reviewed. Medical reports of all selected patients were assessed to collect demographic information such as age, sex, clinical symptoms, PA size, the extent of PA extension and resection, outcomes and complications. Patients with large PAs had improvement in visual improvement (78.1%; 50/64), gross total resection (84.4%; 54/64) compared to patients with giant PAs who had improvement in visual (71.2%; 42/59) and gross total resection (74.6%; 44/59). The rate of CSF leakage was 7.8% and 23.7% for large and giant PAs (p=0.0399). After a mean follow-up period of 40.8 (6-75) months, 10 (15.6%) patients with large PAs experienced tumor recurrence, while 2 giant PA patients (3.4%) experienced tumor recurrence after a mean follow-up period of 40.6 (3-70) months (p=0.0314). Resection of both large and giant pituitary neuroendocrine tumors by microscopic trans-sphenoidal surgery may be safe and effective surgical technique with low morbidity and mortality ²⁾.

Thirty-five patients were operated between 2000 and 2010. Suprassellar extension of the tumors were classified according to Hardy and Mohr based on magnetic resonance (MR) studies. Pituitary endocrine function and MR scans were assessed preoperatively and at 1, 6, and 12 months postoperatively. Immunohistochemical studies were based in regard to the expression of the proliferative Ki-67 index and the hormonal receptor for luteinizing hormone, follicle stimulating hormone, growth hormone, thyroid stimulating hormone, adrenocorticotropic hormone, and prolactin. Tumors specimens were obtained from 35 patients with GNFPA. Endoscopic transsphenoidal surgery was the approach of choice.

Thirty-five patients were submitted to 49 surgeries, 44 (89.8%) were transsphenoidal and 5 (10.2%) were transcranial. The most frequent preoperative complaints were visual acuity impairment and visual field defect in 25 (71.2%) and 23 (65.7%) cases, respectively. Improvement of visual acuitiy and visual field deficit after surgery was seen in 20 (80%) and 17 (73.9%) patients, respectively. Endocrinological deficits were encountered in 20 patients (57.1%). After surgery, 18 patients (51.4%) required hormonal replacement. Three patients had visual symptoms related to pituitary apoplexy and recovered after surgery. The Ki-67 labeling index (LI) ranged from <1% to 4.8%. The rate of recurrence in tumors with Ki-67 <3% was 7.7% (2 patients), Ki-67 >3% was present in 5 patients and the recurrence committed 3 patients.

In our series, regardless the improvement of visual function and compressing symptoms, 5 patients with expression of Ki-67 LI more than 3% experienced a recurrence ³⁾.

A retrospective data analysis of all patients who underwent transsphenoidal endonasal endoscopic surgery at the General Hospital of Fortaleza, Brazil, between January 1998 and November 2011 was performed. Patients who presented with pituitary neuroendocrine tumors larger than 4 cm were included in the study. Analysis of factors related to the choice of the operative approach, hormonal and visual status, extent of resection, tumor control rates, clinical outcome, and complications were evaluated.

Fifty cases (10.41%) matched our inclusion criteria. Nonfunctioning tumors were present in 42 patients (84%); among functioning adenomas, five patients (10%) had growth hormone-secreting adenomas, and three patients (6%) had prolactinomas. Total removal of the tumor occurred in 19 cases (38%), near-total removal in 9 cases (18%), and partial removal in 22 cases (44%). Postoperative cerebrospinal fluid leaks occurred in four cases (8%). Postoperative diabetes insipidus was present in 10% and new anterior pituitary insufficiency affecting one axis or more than one axis was observed in 22% and 14%, respectively. The presence of Knosp score ≥3 was associated with subtotal resection. Patients harboring hormonally active adenomas were submitted to adjuvant medical therapy for long-term clinical control. Vision improved in 38 patients (76%), with only one case of visual deterioration reported.

Transsphenoidal endoscopic endonasal surgery may provide effective treatment for patients with giant adenomas when performed by a surgical team that specializes in pituitary surgery. In cases in which total resection by the endoscopic approach may be associated with important complications, we advocate the use of partial resections followed by adjuvant drug therapy or radiotherapy. In cases of progressive enlargement of residual lesions, a second endoscopic debulking of the tumor may be considered for control of the disease ⁴⁾.

Two hundred and fifty patients with giant pituitary neuroendocrine tumors were managed surgically at the Department of Neurosurgery, Neurosciences Centre, All India Institute of Medical Sciences, New Delhi, India over last 13 years. Majority (92%) of patients presented with visual deterioration. Non-functioning tumors were found in 136 patients (54.3%). Among functioning adenomas, 63 patients (25.4%) had prolactinomas and 45 patients (18%) had GH-secreting adenomas; while 3 patients each had LH and ACTH- secreting adenomas. The maximum tumor diameter varied from 4 to 10.5 cm, with mean diameter of 5.4 cm. The factors determining choice of operative approach and surgical outcomes in these tumors were analyzed.

Overall, 273 surgical procedures were performed in 250 patients. Of these, 110 were transsphenoidal, while 163 were transcranial approaches. A single surgical procedure was performed in 227 patients (89.2%). 23 patients (9.2%) underwent re-exploration either because of postoperative apoplexy or residual tumor. Overall, near total (>90%) tumor excision could be achieved in 74%, with improved vision in 53% and good outcome in 75% patients. The mortality and morbidity were 4.4% and 14%, respectively.

The main goal of surgical treatment of giant pituitary neuroendocrine tumor is maximum possible tumor extirpation with minimal side effects, which can be achieved by careful preoperative planning of operative approach, based on directions of tumor extensions and invasiveness. Maximal surgical removal of giant adenomas offers best chances to control tumor growth when followed with adjuvant medical and radiation therapies ⁵⁾.

Clinical data of 160 giant pituitary neuroendocrine tumor patients were analyzed. Of the 160 patients, 90 received total tumor removal, 70 received subtotal tumor removal combined gamma knife radiation. The symptom improvement, tumor size change, serum hormone concentration, complications after treatment, and so on, of the 2 groups were compared.

At 12 months after treatment, the efficiency rate, recurrence rate, and mortality were 74.4%, 31.1%, and 3.3%, respectively, in total tumor removal group; however, the efficiency rate reached 91.4%, the recurrence rate decreased to 11.4%, and no patients died in combined therapy group. The follow-up results at 24 months after treatment and at present (over 5 years) showed that though the efficiency rate had descended and recurrence rate or mortality had ascended in both groups, the efficacy of combined therapy was obviously better than that of total tumor removal. The decrease of serum hormone concentration was more obvious in combined therapy group than in total tumor removal group at 12 months after treatment. Moreover, total tumor removal group had more serious complications than combined therapy group after treatment.

Subtotal tumor removal combined gamma knife radiation is better than total tumor removal for giant pituitary neuroendocrine tumor ⁶⁾.

Between 1990 and 2004, 95 patients with a giant pituitary neuroendocrine tumors underwent surgery at the Department of Neurosurgery, University of Brescia, Italy. Nonfunctioning pituitary neuroendocrine tumor was the most frequent type (n = 70; 73.7%), whereas hormone-secreting adenomas numbered only 25 (26.3%). The mean age at the time of surgery (+/-standard error of the mean) was 48.4 +/- 1.5 years; there were 66 men (69.5%) and 29 women (20.5%).

In total, 111 surgical procedures were performed. Of these, 85 approaches (76.6%) were transsphenoidal and 26 (23.4%) were transcranial. Visual improvement occurred in 59 of the 79 patients with preoperative defect who could be evaluated after surgery (74.7%). Radical tumor excision was obtained in 14 patients (14.7%). Adjuvant medical and radiation therapies led to 74.5% (95% confidence interval, 62.7-86.4%) control of tumor growth at 5 years. This was not different in patients with nonfunctioning pituitary neuroendocrine tumors compared with patients with hormone-secreting tumors. In the subgroup of patients with nonfunctioning pituitary neuroendocrine tumors, radiation therapy had a protective role against tumor growth (P < 0.01).

Maximal surgical removal of giant adenomas through the transsphenoidal or transcranial approach, or both, aimed to relieve compression of the optic pathway and reduce tumor volume as much as possible, offers the best chances to control the tumor when followed with adjuvant medical and radiation therapies ⁷⁾.