Clinical study of endoscopic treatment of a sellar pituitary adenomas with sellar diaphragm defect

Pituitary adenoma is the most common tumor in the sellar region. The incidence of intracranial tumors ranks third, accounting for 10 to 15%, among all intracranial tumors [1, 2]. Studies have shown that the prevalence of pituitary tumors is about 5/100000 [3, 4]. Pituitary adenomas smaller than 10 mm are generally called pituitary microadenomas, those that are 10–30 mm tumors are called pituitary macroadenomas, and tumors larger than 30 mm are called pituitary giant adenomas [1].

Currently, there are two ways to grade pituitary adenomas using preoperative MRI. one is the Knosp classification [5]. This grading criterion is based on the position of pituitary adenomas relative to the internal carotid artery. The other is the modified Hardy classification (hereafter referred to as “Hardy classification”), which is used when pituitary adenomas break through the suprasellar cistern. The Hardy grading standard describes the degree of suprasellar extension of the tumor: Grade 0, the tumor remains in the saddle; Grade A, the tumor expands to the suprasellar cistern; Grade B, recessus opticus block; Grade C, the third ventricle is significantly displaced; Grades D are defined as the extent of the tumor above 20 mm on the sphenoid bone [6]. Large pituitary adenomas and pituitary giant adenomas usually protrude from the saddle area or even to the front of the skull base or the third ventricle [7]. According to the Hardy classification, tumors above the suprasellar cistern are referred to as suprasellar pituitary adenomas. However, in actual clinical work, a very small number of patients with saddle pituitary tumors have a congenital diaphragm sella turcica defects or serious defects in the diaphragm sella turcica. These conditions make the tumors originating in the sella have no pressure effect, and they grow irregularly to the suprasellar region. The tumor can invade the optic chiasma forward and squeeze the third ventricle floor upward. We call this a suprasellar pituitary adenoma with defect of sellar diaphragm (SPADSD). Non-functional pituitary tumors are diagnosed when the volume grows to a large extent and causes symptoms such as decreased vision [8, 9].

Transsphenoidal surgery is a commonly used to treat pituitary adenomas [10‐13]. In recent years, there has been popular application of neuroendoscopy. This technique has the advantages of clear visual field, less blind area, less trauma, flexible observation angle, high total tumor resection rate, rapid recovery after surgery, and others. The endoscopic endonasal approach (EEA) has become the main surgical method for resection of pituitary adenomas [14]. Its excellent postoperative results have shown that this surgical procedure is effective not only for saddle adenomas but also for the giant pituitary adenomas invading the suprasellar region. At present, EEA is the treatment of choice for pituitary tumors that invade the suprasellar region [15].

Nevertheless, it is unclear whether EEA is safe and effective for treatment of SPADSD. Therefore, this article describes the clinical features of 19 patients with SPADSD treated with endoscopic surgery. We elucidated the imaging and anatomical features of these tumors to distinguish them from other tumors, summarizing the problems that should be addressed during surgery, and evaluating the efficacy of EEA.

All 19 patients underwent surgery using EEA. During the procedure, we confirmed that these patients suffered from congenital loss of the diaphragm sella turcica (Fig. 1a, b), causing the tumor to invade from the saddle to the suprasellar region. Because growth characteristics and MRI signal feedback are similar to those of many common tumors in the saddle area, it is easy misdiagnose the tumor preoperatively (Fig. 2). Compared with the integrity of the sellar diaphragm, the defect of the diaphragm sella turcica allows growth of the tumor to be unrestricted; therefore, it is more likely to invade tissues of the suprasellar region such as the optic nerve. However, in clinical practice, we found that some non-functional pituitary tumors are invasive, they can break through the diaphragm sella turcica and grow into the suprasellar region. Because of the characteristics of this tumor, the growth pattern of this kind of pituitary tumor is easily confused with SPADSD (Fig. 3). As we can see in Fig. 3, because the tumor always originates in the Sellar region, and the diaphragm sella turcica above the tumor hinders the growth of the tumor to the suprasellar region, it will oppress the hypophysis and so on. It is difficult to find the normal shape of the pituitary gland in the MR image, even the flattened pituitary gland can not be found (Fig. 3a, b). When the diaphragm sella turcica is destroyed, it will provide a small channel for non-functional pituitary tumors to grow into the suprasellar region. But the diaphragm sella turcica is almost not completely destroyed, so we will find a waist-shaped shape of the tumor on the level of the diaphragm sella turcica on MR images (Fig. 3a, b). Through the images during the operation, we did find the existence of the diaphragm sella turcica and confirmed our conjecture (Fig. 3c, d).

After the operation, 6 patients developed symptoms of cerebrospinal fluid leak (CSF). Four of patients recovered on their own within 3 days after the occurrence of CSF, the other two patients had no improvement in the symptoms of CSF and developed symptoms of infection such as fever and chills, so we performed surgery on these two patients to repair CSF. All 19 patients were discharged from hospital and there were no deaths due to factors such as intracranial infection (Table 1).

Patient 1 is a woman (Fig. 4a, b). One month before the operation, the patient developed bilateral blurred vision and a right-sided vision defect; nevertheless, she did not undergo treatment. One week before the operation, the patient suddenly developed a sharp headache with blindness in the right eye. After two hours, the patient’s symptoms improved spontaneously. Before the operation, we performed brain MRI, as well as eye, pituitary and thyroid function hormone tests. We first ruled out diseases of the eye. Because pituitary-related hormones were within normal ranges, the tumor was thought to be a non-functional pituitary adenoma. After completing the relevant examinations, we performed surgery. During the operation, we used the grinding stone to remove saddle bone, and identified the dura mater (Fig. 4d). We used TCD to determine the position of blood vessels and the cut the dura mater sharply, revealing the tumor. The texture of the tumor was soft (Fig. 4e). The pituitary morphology remaind intact during the operation. After the tumor was completely removed, no damage was caused to the surrounding optic nerve and anterior cerebral artery (Fig. 4f). We used a middle turbinate pedicled mucosal flap, artificial dura mater and fibrin-thrombin glue to repair the area. After surgery, the patient’s visual acuity improved significantly, and the visual field defect on the right side resolved. On the fourth day after surgery, the patient developed symptoms of cerebrospinal fluid (CSF) leak; however, there were no symptoms related to intracranial infection. After repair of the CSF leak, the patient had no more symptoms referable to the CSF symptoms. There was no hypophysis dysfunction after the operation. The patient was discharged from the hospital on the 10th day after surgery. Pathology after surgery confirmed that the tumor was a pituitary adenoma. Immunohistochemical index of pathology: CK(+), ACTH(±), HGH(−), PRL(−), Synaptophysin(+), P53(−), Ki-67(5%+) (Fig. 4c).

Patient 2 is a man (Fig. 5a, b). The patient had a first operation in another hospital two years prior because of dizziness and palpitations. The surgery consisted of removal of 10% of the tumor. The patient had decreased visual acuity one month prior to admission to our hospital. After MRI, it was determined that the tumor had recurred. We tested hormones related to pituitary and thyroid function before surgery, revealing FT4: 27.68 pmol/L, FT3: 14.84 pmol/L, TSH: 5.24 mIU/L; all of which were higher than the normal values of 8.63 pmol/L, 9.14 pmol/L and 0.29 mIU/L, respectively. After we excluded diseases related to the eyes and heart, we performed surgery. We ground off the saddle bone, and identified the dura mater directly. After we used TCD to determine the position of the blood vessels, we used microsurgical scissors to sharply cut the dura mater and identify the tumor (Fig. 5). The tumor was tough and its blood supply was abundant. We bluntly separated the tumor from the surrounding important anatomical structures, and found that the pituitary morphology remained intact during the operation. After tumor resection, the optic nerve, anterior cerebral artery and the third ventricle were clearly seen to be free of damage (Fig. 5e, f). We used a middle turbinate pedicled mucous flap, artificial dura mater, and fibrin-thrombin glue to repair the surgical area. Postoperative self-reported visual acuity improved after surgery. On the third postoperative day, we performed pituitary-related hormone and thyroid function tests, notable for FT4: 18.73 pmol/L, FT3: 3.30 pmol/L, and TSH: 0.71 mIU/L. These three indicators were all within the normal ranges. Postoperatively the patient had no symptoms of CSF leak, intracranial infection, or hypophyseal dysfunction. The patient was discharged from the hospital on the 7th postoperative day. The pathology after surgery confirmed that the tumor was a pituitary adenoma. Immunohistochemical index of pathology: CK(+), ACTH(−), HGH(+), PRL(−), Synaptophysin(+), P53(−), Ki-67(10%+), S-100(−) (Fig. 5c).

Patient 3 is a woman (Fig. 6a, b). The patient began to experience vision loss one year prior. In the two weeks prior to admission, her visual acuity degraded severely. Only some light could be seen before surgery, and no objects in front of the eyes could be seen. After exclusion of eye-related diseases, the patient underwent MRI, revealing high likelihood of a pituitary tumor. Before the operation, we performed examinations of pituitary and thyroid function-related hormones; all hormones were within the normal ranges. During surgery, we used a grinding drill to open the saddle bottom. After the bone was removed, revealing the dura mater (Fig. 6a, b). After using TCD to determine the position of the blood vessels, the dura mater was sharply cut, revealing that the tumor texture was soft and the blood supply was not abundant (Fig. 6e). The tumor was completely removed under microscopy. The optic nerve and the anterior cerebral artery were shown to be intact and the pituitary morphology remained intact (Fig. 6f). We used a middle turbinate pedicled mucosal flap, artificial dura mater, and fibrin-thrombin glue to repair the area. On the second day after surgery, the patient could see objects in front of his eyes. There were no CSF leak, intracranial infection, or hypophyseal dysfunction after surgery. The patient was discharged from hospital on the 7th day. Pathologically confirmed after surgery that the tumor was a pituitary adenoma. Immunohistochemical index of pathology: CK(+), ACTH(−), HGH(−), PRL(±), Synaptophysin(+), P53(−), Ki-67(3%+) (Fig. 6c).

We followed up 19 patients half a year after the operation. None of the 19 patients had recurrent CSF, only one patient had no obvious recovery of visual impairment, and only one patient had hypofunction of hypophysis.

Through our study, we found that it can be judged before operation according to the characteristics of SPADSD, and reduce the probability of wrong diagnosis. SPADSD often grows on the saddle because there is no physical restraint. These tumors do not compress the pituitary, but rather they grow toward the upper unrestricted area. On MRI, we often note that the shape of the pituitary is normal. Nevertheless, the shape of the SPADSD is usually irregular, showing a lobular shape. There are few violations of the pituitary during surgery, and there are fewer cases of hypofunction of the pituitary after surgery.

SPADSD is an invasive pituitary tumor that manifests in several invasive modes. It can break through upwards towards the saddle to invade the anterior skull base or the third ventricle, and can invade the cavernous sinus or can surround the internal carotid artery growing to the saddle sides. At present, there is no relevant research demonstrating which surgical method is more suitable for the resection of the SPADSD. We combined with the advantages of endoscopic techniques to conduct an in-depth discussion and review of the treatment of this tumor. The growth patterns and imaging signals of SPADSD are often very similar to those other intracranial tumors; therefore, the clinician often has difficulty with the preoperative diagnosis and the choice of surgical methods. Below, we compare the characteristics of other common tumors in the sellar region with those of SPADSD, in hopes of reducing the misdiagnosis, better understanding their common growth patterns, and developing better treatment schemes.

SPADSD has different features from other tumors growing in the suprasellar region, including growth pattern, imaging features, surgical features, etc. We discussed SPADSD in detail, and compared its growth patterns and imaging characteristics with those of similar intracranial tumors. After summarizing the surgical procedures of 19 patients, we believe that EEA is the preferred surgical approach to removal of such tumors.