Pituitary NeuroEndocrine Tumor with temporal pallor – Case report and literature review

Carotid-cavernous fistula after partial maxillectomy: Case report

BackgroundThe 5th edition of WHO classification (WHO5) renamed pituitary adenoma as pituitary neuroendocrine tumor (PitNET), aligning with NET nomenclature from other sites. This study investigated the clinicopathological characteristics of surgically resected PitNET based on the WHO5 classification.MethodsA retrospective analysis was conducted on 210 cases of surgically resected and pathologically confirmed PitNET treated at Seoul National University Hospital from 2021 to 2023. The tumors were graded using the French five-tiered grading system proposed by Trouillas et al. Detailed information on grade 3 metastatic PitNET cases is provided.ResultsThe cohort’s median age was 53 years (age range: 8–84 years), with a male-to-female ratio of 1:1.1. Mean tumor size was 2.5 cm (range: 0.1–6.5 cm). Macroadenomas predominated (91.9%), followed by microadenoma (6.7%), and giant tumors (1.4%), with 56.2% extending suprasellarly. SF1-lineage PitNET was most prevalent (49.5%), followed by PIT1-lineage (23.3%) and TPIT-lineage (17.1%). Null cell tumors (5.7%) and unclassified plurihormonal PitNET (4.3%) were rare. PIT1-lineage PitNET comprised somatotrophs (47.0%), mature plurihormonal PIT1 lineage tumors (18.4%), thyrotrophs (16.3%), immature PIT1-lineage tumors (16.3%), and acidophilic stem cell tumors (n=1), however, there was no lactotroph PitNET. Among SF1-lineage tumors, serologically non-functional tumors predominated (79%), while, immunohistochemically, 71.2% were gonadotrophin (FSH/LH)-positive. Tumor grades by the French five-tiered classification system were distributed as follows: grade 1a (58.1%), 1b (17.6%), 2a (16.2%), 2b (7.1%), and 3 (1.0%). Two cases of metastatic corticotroph PitNET were observed: The first case, a 50-year-old female had liver metastasis and experienced tumor recurrence 7 years after his initial diagnosis of PitNET, ultimately dying 9.5 years later. The primary tumor appeared bland, but the metastatic tumor exhibited a high mitotic rate and a Ki-67 index was 48%. The second case involved a 44-year-old man with metastases to the paranasal sinus, liver, and bone. Despite showing initial bland histopathology and a low proliferation index, this tumor displayed aggressive behavior. The patient had a recurrence 1.5 years after diagnosis, with additional metastases emerging 3 years later. He survived for 8.0 years and is currently disease-free following surgery, chemotherapy, and radiotherapy.ConclusionThis comprehensive analysis of surgically resected PitNETs using the new WHO5 classification provides valuable insights into the distribution of the subtypes in the surgical cohort. Key findings were the predominant gonadotroph PitNET, the absence of lactotroph PitNET, and the rarity of null cell tumors in surgical cases. The lack of lactotrophs was mainly due to medical treatment. This study highlights the discrepancy between serological and immunohistochemical findings of SF1-lineage PitNETs. While metastatic PitNET cases showed poor prognosis, the predictive value of the French grading system for PitNET requires further validation through extended follow-up.

The etiological basis of pituitary neuroendocrine tumors is uncertain. We used Mendelian randomization technique to investigate the potential influence of several risk factors on the likelihood of developing pituitary neuroendocrine tumors. We admitted 8 risk factors, divided into 3 lifestyle factors and 5 chronic diseases as exposure factors. We used weighted median, simple model, weighted model, inverse-variance weighted, and the MR-Egger regression method for causal effect estimations and sensitivity analyses. We observed that genetically forecasting increased moderate to vigorous physical activity levels (OR = 5.21 [1.38–19.72], P = .015) was linked with a higher incidence of pituitary neuroendocrine tumors. Allergic disease (asthma, hay fever, or eczema) (OR = 0.81 [0.66–0.99], P = .039), chronic kidney disease (OR = 0.67 [0.50–0.90], P = .008), increased sleep duration (OR = 0.07 [0.01–0.37], P = .001), and types of physical activity (e.g., swimming, cycling, keeping fit, and bowling) (OR = 0.02 [0.01–0.66], P = .029) were connected with lower incidence of pituitary neuroendocrine tumors. There was no evidence that the other 3 risk factors notably correlated with pituitary neuroendocrine tumors. This study provides evidence that allergic diseases, chronic kidney disease, sleep duration, and physical activity are associated with the development of pituitary neuroendocrine tumors. The findings highlight the importance of reconsidering causality in epidemiological studies to better understand risk factors and prevention strategies for pituitary neuroendocrine tumors.

ABSTRACTBACKGROUND: Endoscopic transnasal surgery has gained rapid global acceptance over the last two decades. The growing literature and understanding of anterior skull base endoscopic anatomy, in addition to new dedicated endoscopic instruments and tools, have helped to expand the use of the transnasal route in skull base surgery.OBJECTIVE: Report our early experience in expanded endoscopic transnasal surgery (EETS) and approach to skull base neoplasms.DESIGN: Descriptive, retrospective case series.SETTING: Major tertiary care center.PATIENTS AND METHODS: A retrospective case review was conducted at King Saud University Medical City between December 2014 and August 2019. Cases with skull base neoplasms that underwent EETS were included. EETS was defined as endoscopic surgical exposure that extended beyond the sellar margins (prechiasmatic sulcus superiorly, clival recess inferiorly, cavernous carotid lines laterally). Routine transsphenoidal pituitary neoplasms, neoplasms of sinonasal origin and meningoencephaloceles were excluded.MAIN OUTCOME MEASURES: Preoperative clinical assessment, imaging results, surgical approach, and hospital course were all retrieved from the patient electronic charts. Clinical follow-up, perioperative complications, and gross residual tumor rates were documented and reviewed.SAMPLE SIZE AND CHARACTERISTICS: 45 cases of EETS, 13 males and 32 females with mean age of 39.0 (17.7) years (range 2–70 years).RESULTS: The series comprised a wide range of pathologies, including giant pituitary adenoma (8 cases), meningioma (23 cases), craniopharyngioma (4 cases), chordoma (4 cases), optic pathway glioma (2 cases), epidermoid neoplasms (2 cases), astrocytoma (1 case), and teratoma (1 case). For the entire series, gross total resection was achieved in 25/45 operations (55.5%). Postoperative cerebrospinal fluid leak was the most common complication observed in 9 patients (20%) which were all managed endoscopically. Major vascular complications occurred in 2 patients (4.4%) and are described. Other complications are outlined as well. No mortality was observed.CONCLUSIONS: EETS to the skull base can be done with results comparable to traditional approaches. More work is needed to expand our experience, improve outcomes, and educate the public and medical community in our region about the usefulness of this approach.LIMITATIONS: Sample size and study design.CONFLICT OF INTEREST: None.

The uncommon aggressive pituitary tumors are named carcinomas when metastases are detected, either in the central nervous system and/or systemically. Some cases are associated with hormonal overproduction, but most are diagnosed because of local symptoms. These neoplasias are generally refractory to current treatments. A 51 year-old woman presented sudden onset of headache, left arm paresis and left facial hypoesthesia. Computed tomography scan and magnetic resonance imaging revealed a pituitary tumor invading the left sphenoidal and cavernous sinuses. Laboratory data excluded hormonal hypersecretion. The patient underwent transsphenoidal surgery and histological findings showed a neoplasia with Ki-67 estimated at 75%. Medical imaging excluded both a primary occult tumor and central nervous system or systemic dissemination. Three weeks postoperatively, neurological condition worsened, with new onset of ataxia, bilateral ptosis, ophthalmoplegia and an increase in the size of the lesion, leading to surgical intervention by craniotomy, followed by only a few sessions of radiotherapy, because of severe disease progression. Patient died nearly 2 months after the initial manifestations. This case illustrates the aggressiveness of some pituitary lesions, the limited efficacy of current treatment modalities such as surgery or radiotherapy and the pitfalls of the current pituitary tumors classification. To our knowledge, this case corresponds to one of the most aggressive pituitary neoplasms reported so far, with a very high Ki-67 index (75%) and short survival (2 months). Ki-67 index could be of prognostic value in pituitary tumors. Pituitary tumors World Health Organization (WHO) classification could be revisited.

The incidence of pituitary neuroendocrine tumors has been reported high at autopsy. This study aimed to detect many tumors in both anterior and posterior lobes to prove tumor histogenesis. In total, 150 pituitary glands were studied from the University of Kansas Medical Center from 1995 to 2000. The pituitary gland was sagittally sliced from anterior to posterior into 6 to 8 sections. When H&E-stained sections revealed tumors, the tumors were immunohistochemically stained for 6 pituitary hormones. Among 150 autopsy cases, 38 (25.3%) harbored microadenomas, including 4 cases with double tumors. Twenty-three (54.7%) cases were negative to all pituitary hormones. Of the remaining 19 tumors, 13 (30.9%) were lactotrophs, with 4 cases being concomitantly somatotrophs and gonadotrophs, and 2 cases were corticotropes. More than 85% of pituitary neuroendocrine tumors were adjacent to the capsule. Thirteen (8.7%) granular cell pituicytomas were found in the posterior lobe. There were pituicytes transforming into granular cell tumors. The incidence was 25.3% for pituitary neuroendocrine tumors and 8.7% for granular cell pituicytomas. Since most pituitary neuroendocrine tumors were adjacent to the pituitary capsule, the capsule appeared to be the germinal center. Both pituitary tumors belonged to the 2 different transcription factor lineages.

IntroductionPituitary adenomas are the most common lesions of the sellar region. The most common (40%) functional pituitary adenomas are prolactinomas. Craniopharyngiomas are epithelial tumors of embryonal origin originating from Rathke's sac. Very few cases of collision tumors co-existing with pituitary adenoma and craniopharyngioma have been described in the literature.Clinical CaseWe present a case of histopathologically proven craniopharyngioma accompanying prolactinoma in a 63-year-old female patient diagnosed with prolactinoma 40 years ago. She was treated with bromocriptine after the diagnosis, and the treatment was switched to cabergoline four years later. Although the biochemical remission was achieved, there was no significant decrease in tumor size. She had not received any treatment during last 4 years before the administration. She was admitted to our clinic with a complaint of headache. Her serum prolactin level was 1550 ng/ml ((Reference:4,79-23 ng/ml). According to the pituitary Magnetic Resonans Imaging(MRI); reports were as follows in 2007; an isolated 8x6x13 mm adenoma was observed, and then in 2015; another cystic lesion (craniopharyngioma?) was detected adjacent to the infindibular stalk in addition to the defined pituitary adenoma (Figure 1a). In the last pituitary MRI (2022); a cystic lesion extending from the sellar cavity to the suprasellar cistern and a solid mass lesion located left to the cavernous sinus, was observed (Figure 1b). Upon a dramatic increase of the tumor volume on pituitary MRI, she underwent pituitary surgery. The histopathological diagnosis was adamantinomatous craniopharyngioma. Postoperative prolactin level decreased to 10 ng/ml. Since prolactin levels decreased after the diagnosis of craniopharyngioma, the surgical material was re-evaluated by the pathologist. No evidence of prolactinoma was found. Significant regression was observed in the patient's 1st month follow-up pituitary MRI compared to the preoperative MRI. Postoperatively, prolactin levels remained within the normal range for the first 6 months. After the 6th month, cabergoline treatment was started when prolactin levels increased to 497 ng/ml.ConclusionPituitary adenoma and craniopharyngioma collision tumors are extremely rare. Only 6 patients with the coexistence of craniopharyngioma and prolactinoma have been reported in the literature, including our case. Histopathological diagnosis may be necessary to differentiate craniopharyngioma from cystic macroprolactinoma.Figure 1:Magnetic Resonans ImagingFigure 1: a. Post-contrast coronal pituitary MRI examination revealed a pituitary adenoma (thick arrow) located in the left cavernous sinus. aAnother cystic mass lesion (thin arrow) was detected adjacent to the infindibular stalk.; b. Coronal contrast-enhanced pituitary MRI image showed cystic (arrow) and

Objective To evaluate the magnetic resonance imaging (MRI) and biological marks in pituitary adenomas with cavernous sinus invasion.Methods The MRI features and intraoperative findings were investigated in 45 patients with pituitary adenoma,and their specimens of pituitary adenomas were analyzed for the expression of F8,Ki-67,VEGF,MMP-9,nm23,c-myc and bcl-2 immunoreactivity using immunoperoxidase staining.MVD was assessed using F8-related antigen.Results The sensitivity of MRI for predicting cavernous sinus invasion was 60%,its specificity 85%,its positive predictive value 83% and negative predictive value 63% in 45 patients with pituitary adenoma.The results of immunoreactivity revealed that MVD,Ki-67 label index (LI),the expression of VEGF and MMP-9 of invasive pituitary adenomas were significantly higher than those of noninvasive (52.52±11.18 vs 34.96±18.69,2.74±2.83 vs 1.25±1.45,4.73±0.64 vs 3.09±1.48 and 3.05±1.04 vs 0.67±0.74,P0.001,=0.039,0.001 and 0.001,respectively).The expression of nm23 of noninvasive pituitary adenomas was significantly higher than that of invasive (4.08±1.18 vs 1.55±1.52,P0.001).But c-myc LI and bcl-2 expression had no association with invasiveness of pituitary adenomas (1.07±1.54 vs 0.35±0.73,P=0.061;2.34±1.75 vs 1.66±1.79,P=0.201,respectively).Conclusion Pituitary adenomas with cavernous sinus invasion can be diagnosed by sensitive gadolinium-enhanced MRI preoperatively.MVD and the expression of Ki-67,VEGF,MMP-9 and nm23 have associations with invasiveness of pituitary adenomas to some extent.These markers may provide some useful information to the treatment of invasive pituitary adenoma.

Ectopic pituitary adenomas are exceedingly rare entities that are often misdiagnosed. The resulting delay in diagnosis may be particularly concerning in the case of Cushing syndrome caused by an ectopic adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma. Although the total resection of ectopic adenomas results in rapid and durable remission, persistent Cushing syndrome is often associated with permanently damaging invasive procedures and significantly higher risk of mortality. The authors report the case of a 48-year-old man with ACTH-dependent Cushing syndrome. On the morning before surgery, his serum cortisol measured 51 μg/dl, his ACTH level was 195.7 pg/ml, and his urinary free cortisol level was 2109 μg/day. Serum cortisol was not suppressed with the administration of high-dose dexamethasone. Imaging showed separate masses in both the sphenoid sinus and the pituitary gland, complicating the diagnostic process and requiring pathological assessment of both masses. No other abnormalities were found on thoracic, abdominal, or pelvic scans. Gross-total resection of both lesions was accomplished via an endoscopic endonasal transsphenoidal approach. Pathology confirmed an ectopic ACTH pituitary adenoma of the sphenoid sinus and a Crooke hyaline change of the pituitary gland. The patient achieved stable hormonal remission without significant postoperative complications, returned to full activity within 3 months, and remained disease free nearly 1 year after tumor resection. In a systematic literature review, the authors identified 41 cases of ectopic ACTH-secreting pituitary adenomas, including 18 arising in the sphenoid sinus without direct involvement of the sella. Including the case described here, the total number of ectopic ACTH pituitary adenomas arising in the sphenoid sinus was 19, and the total number of ectopic ACTH pituitary adenomas without regard to location was 42. For the 19 patients with adenomas found in the sphenoid sinus, ages ranged from 16 to 76 years, and there were 15 women and 4 men. The mean and median diameters of the resected sphenoid masses were 13.9 and 8 mm, respectively, with a range of 3-55 mm. Seven were microadenomas (< 1 cm). Fifteen of the 19 cases reported serum ACTH and morning cortisol levels, the means of which were 106.7 pg/ml and 32.5 μg/dl, respectively. Gross-total tumor resection was achieved in all patients except one, and in all of them durable hormonal remission of Cushing syndrome was achieved (mean follow-up time 20 months). Ectopic pituitary adenomas are rare but important causes of Cushing syndrome and related endocrinopathies, particularly because of the rapid onset and severity of symptoms with atypical presentation. Ectopic pituitary adenomas, especially those in the nasal cavity, nasopharynx, or paranasal sinuses, are easily misidentified. Any patient presenting with signs and symptoms of Cushing syndrome without any obvious pituitary adenoma or other sources of hypercortisolemia should be thoroughly screened for an ectopic adenoma. However, as with the case presented here, the coincident existence of a sellar mass should not preclude the possibility of an ectopic source. There should be a high degree of clinical suspicion for any mass in the general area surrounding the sella when evaluating Cushing syndrome.

Concomitant pituitary adenoma (PA) and Rathke's cleft cyst (RCC) are rare. In some cases, such PA is known to produce pituitary hormones. A 53-year-old man was admitted to our hospital with a diagnosis of lacunar infarction in the left basal ganglia. Magnetic resonance imaging (MRI) incidentally showed a suprasellar mass with radiographic features of RCC. When he consulted with a neurosurgical outpatient clinic, acromegaly was suspected based on his appearance. A diagnosis of growth hormone- (GH-) producing PA was confirmed from hormonal examinations and additional MRI. Retrospectively, initial MR images also showed intrasellar mass that is compatible with the diagnosis of PA other than suprasellar RCC. The patient underwent endonasal-endoscopic removal of the PA. Since we judged that the RCC of the patient was asymptomatic, only the PA was completely removed. The postoperative course of the patient was uneventful and GH levels gradually normalized. Only 40 cases of PA with concomitant RCC have been reported to date, including 13 cases of GH-producing PA. In those 13 cases, RCC tended to be located in the sella turcica, and suprasellar RCC like this case appears rare. In a few cases, concomitant RCCs were fenestrated, but GH levels normalized postoperatively as in the cases without RCC fenestration. If radiographic imaging shows typical RCC, and PA is not obvious at first glance, the possibility of concomitant PA still needs to be considered. In terms of treatment, removal of the RCC is not needed to achieve hormone normalization.

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

Introduction: Pituitary adenoma producing symptomatic carotid compression of the internal carotid artery without any apoplexy sign would be extremely rare and there was only one report regarding to this condition. Case Presentation: In this case report we have described a 57-year-old woman with a nonfunctional pituitary macro adenoma which has resulted to symptomatic internal carotid occlusion. Magnetic resonance imaging (MRI) revealed a large pituitary adenoma caused tight stenosis of right internal carotid. The patient has also experienced the transient ischemic attack which has confirmed to be the cause of internal carotid artery occlusion by this macro adenoma tumor. There was not any sign of apoplexy at the time of admission and the patient has not shown a history of pituitary adenoma. The patient then has undergone an endonasal transsphenoidal resection because of this nonfunctional pituitary adenoma. Conclusions: Pituitary macro adenoma producing symptomatic internal carotid occlusion might develop to several serious conditions including transient ischemic attack. Urgent surgical procedure might be the best approach to prevent further severe complications in such patients.

Introduction: Intrasellar cavernous hemangiomas constitute an extremely rare group of findings in endocrinological practice. Diagnosis remains challenging due to non-characteristic symptoms and neuroradiological features which may resemble those of pituitary adenomas.Presentation of the Case: We present a case of female born in 1941, diagnosed with a hemangioma cavernosum located in the Sella turcica. In 2004 our patient presented with uncharacteristic symptoms: syncopes and chronic headaches. Computed tomography (CT) of the head revealed an intrasellar hyperdense tumor mass with radiological features suggesting a pituitary adenoma. In 2005 the patient underwent transcranial resection of the sellar mass, with subsequent oculomotor nerve palsy. In histopathological examination, diagnosis of cavernous hemangioma was determined. Between 2005 and 2020 patient was asymptomatic, with multiple follow-up head MRIs scans, showing gradual progression in size of the intrasellar tumor. The patient was consulted by a neurosurgeon, with no direct indications for surgical approach found. Furthermore, due to suprasellar expansion into the direct proximity of the right optic nerve, the patient was disqualified for Gamma-Knife radiotherapy.The last MRI of the hypothalamic-pituitary area in 2020 revealed a polycyclic, homogeneous, 33x31x29 mm mass, filling in the space of the Sella turcica, with strong enhancement after contrast administration. Invasion of the surrounding structures, including the clivus, right cavernous sinus and right trigeminal cave were described. Bilaterally, internal carotid arteries and right optic nerve adhered directly to the lesion. Pituitary gland was compressed by the tumor mass. In July 2020, in order to verify the ambiguous radiological and clinical characteristics of the lesion including tumor regrowth and its invasiveness, a transsphenoidal partial resection was performed. Tissue samples were collected for the histopathological examination, which confirmed the initial diagnosis of cavernous hemangioma originating from the cavernous sinus. During a multidisciplinary tumor board, having taken into consideration relatively stable clinical condition and high risk possible surgical complications, the patient was currently disqualified from neurosurgical re-operation nor radiotherapy. Surprisingly, during whole follow up, patients pituitary function remained unimpaired. A watchful waiting approach, with radiological and endocrinological follow up were scheduled. Conclusion: To date, only few cases of intrasellar cavernous hemangiomas have been reported. Intrasellar hemangiomas may originate from the vascular tissue of the cavernous sinus. Surgical removal remains the recommended treatment modality, but radiosurgery could be a therapeutic option as well. Stable patients with no clinical symptoms may remain in observation.

[Objective]To assess the value of neuronavigation system in surgery for pituitary adenomas in patients with sphenoid sinus dysplasia via single nostril.sphenoid approach.[Methods]Neuronavigation system guided tran-single nostril-sphenoid surgery was performed on 18 patients with sphenoid sinus dysplasia,admitted to our hospital from December 2010 to December 2011;2 patients were without sphenoid sinus,4 with sphenoid sinus fiont ofsella,9 ofsphenoid sinus being separated several rooms,and 3 of excessive gasification to 2 sides of middle cranial fossa.[Results] The positioned accuracy rate was 100％,and total resection rate was 77.8％.Thirteen patients (72.2％) were cured enjoying good endocrine result.No such severe postoperative complications as internal carotid artery and cavernous sinus injuries were noted in all the patients,except that transient polyuria occurred in 4 (22.2％) and CSF leakage in 1 (5.6％).[Conclusion] The neuronavigator-assisted trans-sphenoidal surgery in patients with sphenoid sinus dysplasia is helpful in improving the security of trans-sphenoidal surgery and reducing the local injury and serious complications,which extends the surgical indications to some extent. Key words: Neuronavigation; Sphenoid sinus dysplasia; Endonasal trans-sphenoidal approach; Pituitary adenoma

ABSTRACT. The books on Classic Descriptive and Topographic Anatomy carry out a complete and detailed description of the anatomical accidents (orifices, conducts, fissures, spines, apophysis, tubercules, cavities and pits, crests, sector divisions, internal configuration and mucular and ligamental insertions of the sphenoid bone, necessary to understand our proposal. They also describe their relations with other bones in skull and face, with the hypophysis and with the neurovascular elements that enter or exit from the cranial cavity. In this paper we expect to present and arrange in order of hierarchy the overview of a bone that is key at the cranial base and we propose a division in sectors in accordance to the functions that each one of them plays. We therefore consider that the sphenoid bone is a growth centre of the cranial base, passageway point of neurovascular elements, resistance center together with the occipital bone, center of muscle insertions and continent of the sphenoid sinuses, cavernous sinus and hypophyis gland. Finally, it is a multiarticulated bone and multicavernous, given that it forms cavities in the cranium, in the facies and common to both anatomical sectors. It conforms part of a transnasal tract for the approaching of the Sella Turcica and its contents, the hypophysis. It allows the exit from the cranium of the three branches of the Trigeminal Nerve (V cranial pair), of undoubtable value in dentistry.