Invasive pituitary adenomas are pituitary adenomas that grow through the envelope and invade adjacent structures, often invading the adjacent dura, skull, cavernous sinus and encircling the internal carotid artery bilaterally or unilaterally.
1. Incidence and epidemiology
The incidence of invasive pituitary tumors has been inconsistently reported in the literature, mainly due to the use of different criteria for determining the incidence. The incidence of invasive pituitary tumors has been reported to be approximately 43%, mainly based on imaging and intraoperative findings. The rate of intraoperative tumor infiltration in the saddle base and saddle diaphragm has been reported to be 85%, and is related to the type of tumor pathology, including 69% for microadenoma, 87% for saddle macroadenoma, and 94% for extra-saddle extension macroadenoma. According to a retrospective analysis of 135 pituitary tumors by Luo, 87% developed suprasellarly and compressed the optic cross, 9% reached the hypothalamus and the third ventricle, 28% broke through the saddle base and developed into the pterygoid sinus, and 16% invaded the cavernous sinus. Therefore, the diagnosis of invasive pituitary tumors is not consistent between diagnostic imaging, surgery and saddle-base dural examination. However, in general, invasive pituitary adenomas account for 66%-94% of pituitary adenomas. The proportion of invasive pituitary adenomas to pituitary tumors is highly correlated with the size of the tumor, with the larger the tumor, the higher the proportion, with microadenomas being about 5% of invasiveness, macroadenomas 30%, and macroadenomas almost 100%. Patients with clinically aggressive pituitary tumors are between 30-50 years old, and only about 3-7% of patients are younger than 20 years old. patients with ACTH and PRL pituitary adenomas under 20 years old have a faster growth rate of adenomas.
2.Imaging performance
The diagnosis of invasive pituitary adenoma has been diagnosed by Knosp and Hardy-Wilson grading method, and Hardy’s grading standard for pituitary adenoma is divided into 5 grades.
Grade 1: tumors up to 10 mm in diameter with intra-saddle growth
Grade 2: tumor extends up to 10 mm suprasellar and fills the suprasellar pool
Grade 3: tumor extends 10-20 mm suprasellarly, causing the third ventricle to be elevated;
Grade 4: tumor extends suprasellarly by 20-30 mm, filling the anterior part of the third ventricle
Grade 5: tumor extends > 30mm suprasellarly, reaching the interventricular foramen of the lateral ventricle, often combined with obstructive hydrocephalus.
Grade 1 is a microadenoma, grades 2 and 3 are large adenomas, and grades 4 and 5 are giant adenomas.
In clinical imaging, Kobayash et al. analyzed the factors affecting the MR signal intensity of tumors and concluded that the main factor is the ratio of hormone-secreting positive cells. GH adenoma contains little water, has a high degree of fibrosis and gliosis, shortens Tl and T2 times, and shows iso-Tl and iso-T2 signals. Non-secretory adenomas have a small percentage of hormone-secreting positive cells, but the degree of fibrosis and gliosis is not high, so TWlI is mostly low, slightly low, and equal signal, and T2W I is slightly high, high signal, similar to the signal changes of PRL adenomas. The signal in the tumor can be described by uniformity and inhomogeneity. 95% or more of the area of the tumor has uniform signal, and when >5% of the area has inconsistent signal, the signal is inhomogeneous; signal inhomogeneity is common: 1. 2. cystic lesion: tumor with necrosis, liquefaction or hemorrhage, T1WI shows low signal and T2WI shows high signal; 3.
Wilson classification including extension/suprasellar extension
0: None.
A: Entry into the suprasellar pool.
B: loss of the anterior crypt of the third ventricle.
C: complete displacement of the floor of the third ventricle, with parasaddle extension.
D: intracranial (intradural).
E: into or below the cavernous sinus (extradural).
Invasion/metastasis: intact saddle base, pterygoid destruction, distant metastasis.
The relationship between pituitary adenoma and cavernous sinus was determined by Knosp E et al. using the coronal scan plane of the middle part of the pterygoid saddle (i.e., the middle part of the cavernous sinus) as a reference and the internal, middle, and external tangents between the cavernous sinus segment of the internal carotid artery (C4) and the superior bed process (C2) as markers. Tumors of grades III-IV or C, D, or E are classified as aggressive adenomas using Wilson’s modified Hardy’s classification. The invasive pituitary adenoma can be seen on radiographs as destruction of the surrounding bone at the base of the saddle and dorsum of the saddle, and on CT as infiltrative growth into the saddle. Roax et al. suggested that some of the cavernous sinus invasions diagnosed by CT or MRI were not really invaded by the tumor, but were caused by the tumor compressing the cavernous sinus or protruding into the medial wall of the cavernous sinus in a split-finger pattern; anatomy revealed that nearly 1/3 of the normal pituitary gland protruded into the cavernous sinus. Initially, the specific index for diagnosing cavernous sinus invasion by MRI was that the internal carotid artery was surrounded by the tumor, but later, various criteria were developed.
3. Clinical features
Compared with general pituitary adenoma, the characteristics of invasive pituitary adenoma include.
(1) It is more common in young adult patients, but there are also a large number of reports that there is no obvious direct correlation with age.
(2) They often involve intracranial nerves, erode the adjacent dura and encircle the internal carotid artery bilaterally or unilaterally, and have a high incidence of stroke, which can be as high as 30%.
(3) Clinical symptoms progress rapidly, especially visual acuity and visual field changes are often rapid and severe, which is related to the rapid growth of tumor.
(4) Total surgical resection is difficult, and postoperative radiotherapy and chemotherapy need to be combined; postoperative recurrence rate is high, postoperative complications are heavy, and recurrence time is relatively short. Many studies have shown that postoperative recurrence is significantly associated with the aggressive behavior of the tumor.
(5) Bone destruction is mostly seen in CT examination.
4.Treatment
The ideal therapeutic goals of pituitary adenoma are
(i) To control tumor growth.
(ii) To eliminate or reduce the occupying effect and prevent its recurrence.
③ control the hormone level in the normal range.
④ alleviate the complications caused by hormone secretion disorder.
Imaging cure means that no tumor remains on imaging after surgery; endocrinological cure means that the hormone level overproduced before surgery is restored to normal on the basis of imaging cure. The latter is the ideal standard of cure.
(1) Surgical treatment
The purpose of surgery is to remove the tumor completely or mostly, and to relieve the compression of brain tissue, optic nerve and optic cross by the tumor. At present, the main clinical approaches are transsphenoidal approach and transcoronary single frontal craniotomy approach. Due to the growth characteristics of invasive pituitary tumor and the complexity of surrounding neurovascular, it is difficult to perform total resection, and the recurrence rate is high and the postoperative complications are heavy. Different surgical approaches can be chosen according to the growth pattern of the tumor; for recurrent invasive giant pituitary adenoma, reoperation can relieve the symptoms.
①Coronal cut single frontal craniotomy for pituitary tumor
(2) Single nostril pterygoid sinus approach pituitary tumor resection
③Transpalpebral microscopic combined endoscopic resection of invasive pituitary tumor
At present, there are 5 cases of invasive giant pituitary adenoma in our department, and the use of transsphenoidal sinus microscopic approach combined with neuroendoscopy is very helpful for total resection of the tumor. The advantages of this procedure are that the endoscope has the features of panoramic view and angular observation, which makes the resection of tumor more complete and the protection of important structures more reliable, and less complications. It is less invasive. The surgery can be performed directly and the recovery is fast, and the tumor can be completely resected as far as possible. Endoscopic transsphenoidal resection of pituitary tumor can significantly increase the exposure of surgery and significantly improve the effect of hand.
(2) Drug treatment
Drug therapy is mainly used in prolactin adenoma and growth hormone adenoma. It can directly stimulate the specific D2 receptor on the pituitary cell membrane, inhibit the synthesis and secretion of prolactin, and can reduce or even normalize the prolactin level, reduce the size, disappear the symptoms of lactation, and even restore the gonads and fertility. Most lactomas are sensitive to bromelain. If the effect is not good in 4-6 weeks, surgery should be actively performed, otherwise fibrosis will be easily detected and surgery will be more difficult. Growth inhibitors: mainly used in the treatment of growth hormone adenomas. It can inhibit the synthesis and secretion of growth hormone and inhibit the growth of tumor. Preoperative application can make the tumor softer and smaller, facilitate the operation and postoperative adjuvant treatment, and control the high secretion of growth hormone after operation. The representative drug is octreotide, which is a derivative of growth inhibitor and can inhibit growth hormone more specifically and has stronger biological activity than growth inhibitor. It has been reported that this drug can reduce the growth hormone level to normal in 2/3 of patients with acromegaly, and the tumor shrinks in 20%-50% of patients, and also has therapeutic effect on thyrotropin-secreting adenoma and gonadotropinoma.
(3) Radiation therapy
Since invasive pituitary adenomas often invade the surrounding bone structure, it is difficult to make radical resection of the tumor, and the recurrence rate is easy after surgery, which is 12%-24%. Since Backlund et al. first applied r-knife for pituitary adenoma in the 1970s and achieved satisfactory results, it is believed that gamma knife is safe and effective for pituitary adenoma, especially for postoperative recurrence and postoperative residual tumors in the cavernous sinus or pterygoid sinus. For residual tumors close to the optic cross, the irradiation dose should be controlled to prevent radiological optic nerve injury, and should be avoided in tumors closely related to the optic cross. The analysis of 684 cases of surgically treated pituitary tumors by Oruckaptan et al. showed that radiotherapy was effective for invasive GH adenomas and non-functional adenomas, but not for other types, therefore, postoperative radiotherapy for invasive pituitary tumors is one of the comprehensive clinical treatment measures.
(4) Other treatments
In recent years, temozolomide, a chemotherapeutic agent, has been reported for the treatment of aggressive pituitary adenomas. temozolomide can lower PRL levels and reduce tumor size in aggressive lactogenic adenomas that do not respond to conventional treatment. sheehan et al. found that temozolomide can inhibit cell proliferation and induce apoptosis in aggressive pituitary adenomas. Its efficacy was closely related to the level of MGMT expression in tumors, and temozolomide treatment was sensitive in tumors with low MGMT expression.
In conclusion, the clinical surgical treatment of invasive pituitary adenoma is no longer a problem, but the total resection rate is not high and has a high postoperative recurrence rate. Early diagnosis and surgical resection of the tumor and postoperative comprehensive treatment are measures to reduce recurrence, but how to achieve a complete cure still needs to be studied in depth. With the continuous development of clinical and basic medicine, especially molecular biology and genetic diagnostics, new advances in the diagnosis and treatment of invasive pituitary adenoma will emerge.