Atypical pituitary adenoma: a clinicopathologic case series

2018 ◽  
Vol 128 (4) ◽  
pp. 1058-1065 ◽  
Author(s):  
Martin J. Rutkowski ◽  
Ryan M. Alward ◽  
Rebecca Chen ◽  
Jeffrey Wagner ◽  
Arman Jahangiri ◽  
...  

OBJECTIVEIn 2004, the WHO classified atypical pituitary adenoma as a distinct adenoma subtype. However, the clinical significance of this distinction remains undetermined. The authors sought to define patient characteristics, tumor features, and treatment outcomes associated with atypical pituitary adenoma.METHODSThe authors reviewed records of patients who underwent resection of pituitary adenoma at the University of California, San Francisco, between 2007 and 2014. Per institutional protocol, adenomas exhibiting mitotic activity underwent evaluation for all 3 markers of atypicality (mitotic index, extensive p53 staining, and MIB-1 index ≥ 3%). Statistical analyses were performed using χ2, Fisher’s exact test, t-test, log-rank, and logistic regression.RESULTSBetween 2007 and 2014, 701 patients underwent resection for pituitary adenoma. Among these patients, 122 adenomas exhibited mitotic activity and therefore were evaluated for all 3 markers of atypicality, with 36 tumors (5%) proving to be atypical. There were 21 female patients (58%) and 15 male patients (42%) in the atypical cohort, and 313 female patients (47%) and 352 male patients (53%) in the nonatypical cohort (p = 0.231). The mean age of patients in the atypical cohort was 37 years (range 10–65 years), which was significantly lower than the mean age of 49 years (range 10–93 years) for patients in the nonatypical cohort (p < 0.001). The most common presenting symptoms for patients with atypical adenomas were headaches (42%) and visual changes (33%). Atypical adenomas were more likely to be functional (78%) than nonatypical adenomas (42%; p < 0.001). Functional atypical adenomas were significantly larger than functional nonatypical adenomas (mean diameter 2.2 vs 1.4 cm; p = 0.009), as were nonfunctional atypical adenomas compared with nonfunctional nonatypical adenomas (mean diameter 3.3 vs 2.3 cm; p = 0.01). Among the entire adenoma cohort, larger presenting tumor size was associated with cavernous sinus invasion (p < 0.001), and subtotal resection was associated with cavernous sinus invasion (p < 0.001) and larger size (p < 0.001) on binomial multivariate regression. The median time until recurrence was 56 months for atypical adenomas, 129 months for functional nonatypical adenomas, and 204 months for nonfunctional nonatypical adenomas (p < 0.001). Functional atypical adenomas recurred more frequently and significantly earlier than functional nonatypical adenomas (p < 0.001). When accounting for extent of resection, cavernous sinus invasion, size, age, sex, and functional subtype, atypicality remained a significant predictor of earlier recurrence among functional adenomas (p = 0.002).CONCLUSIONSWhen compared with nonatypical pituitary adenomas, atypical adenomas are more likely to present in younger patients at a larger size, are more often hormonally hypersecretory, and are associated with earlier recurrence. These features lend credence to atypical pituitary adenomas being a distinct clinical entity in addition to a discrete pathological diagnosis.

2020 ◽  
Author(s):  
Yoshikazu Ogawa ◽  
Mika Watanabe ◽  
Teiji Tominaga

Abstract Objective: Pituitary adenoma coexists with intracranial aneurysms in 2.3% to 3.6%, and intracranial aneurysms is thought to be incidental. On the other hand higher age and cavernous sinus invasion are reported to increase the coexistence rate, so these two diseases may be related. Ten males and 14 females with coexistence of pituitary adenomas and intracranial aneurysms were retrospectively investigated among 923 patients (2.6%). Patients were subdivided into two groups with/without direct attachment of cerebral aneurysms to the pituitary adenomas. The clinical characteristics, therapeutic strategies, and possible effects of vascular remodeling factors were investigated.Results: Twelve patients had functioning pituitary adenomas, and cavernous sinus invasion was identified in 7 of 24 patients. Five of these 7 patients were treated with priority for the cerebral aneurysms until 2007, whereas 14 of 17 patients without involvement of the aneurysm tip in the tumor were treated with priority for pituitary adenomas in the later period. Among vascular remodeling factors strong expression of vascular endothelial growth factor (VEGF) was significantly associated with coexistence of pituitary adenoma and cerebral aneurysm (p < 0.05). So VEGF-induced arterial wall remodeling may be part of the mechanism of association between pituitary adenomas and cerebral aneurysms, suggesting possible causative mechanism.


2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Bin Li ◽  
Jianhua Cheng ◽  
Hongyun Wang ◽  
Sida Zhao ◽  
Haibo Zhu ◽  
...  

Abstract Background To investigate the relationship between cyclin B1 (CCNB1) gene expression and cavernous sinus invasion in pituitary adenomas. Methods Twenty-four pituitary adenoma tissue samples were examined by RT-qPCR and Western blot to assess the mRNA expression levels and protein levels of CCNB1, E-cadherin and N-cadherin. Correlation analyses between the expression levels of E-cadherin, N-cadherin and CCNB1 were performed. After lentivirus-mediated knockdown of CCNB1 in rat pituitary adenoma cell lines (GH3 and GT1-1), cell function changes were studied. The relationship between CCNB1 and epithelial-mesenchymal transition (EMT) was further verified by animal experiments. Results CCNB1 and N-cadherin gene expression were significantly higher in the invasive pituitary adenomas than in the non-invasive pituitary adenomas. Conversely, E-cadherin expression in the invasive pituitary adenomas was significantly lower. CCNB1 gene expression was downregulated in the GH3 and GT1-1 pituitary adenoma cell lines; N-cadherin expression was also decreased, but E-cadherin expression was increased. These results were confirmed in vivo. After downregulation of CCNB1, cell invasion and migration was significantly reduced in Transwell experiments. Conclusion High CCNB1 expression in pituitary adenoma affects cavernous sinus invasion through EMT.


2021 ◽  
pp. 1-8
Author(s):  
Salomon Cohen-Cohen ◽  
Ahmed Helal ◽  
Ziying Yin ◽  
Matthew K. Ball ◽  
Richard L. Ehman ◽  
...  

OBJECTIVE Pituitary adenoma is one of the most common primary intracranial neoplasms. Most of these tumors are soft, but up to 17% may have a firmer consistency. Therefore, knowing the tumor consistency in the preoperative setting could be helpful. Multiple imaging methods have been proposed to predict tumor consistency, but the results are controversial. This study aimed to evaluate the efficacy of MR elastography (MRE) in predicting tumor consistency and its potential use in a series of patients with pituitary adenomas. METHODS Thirty-eight patients with pituitary adenomas (≥ 2.5 cm) were prospectively evaluated with MRI and MRE before surgery. Absolute MRE stiffness values and relative MRE stiffness ratios, as well as the relative ratio of T1 signal, T2 signal, and diffusion-weighted imaging apparent diffusion coefficient (ADC) values were determined prospectively by calculating the ratio of those values in the tumor to adjacent left temporal white matter. Tumors were classified into three groups according to surgical consistency (soft, intermediate, and firm). Statistical analysis was used to identify the predictive value of the different radiological parameters in determining pituitary adenoma consistency. RESULTS The authors included 32 (84.21%) nonfunctional and 6 (15.79%) functional adenomas. The mean maximum tumor diameter was 3.7 cm, and the mean preoperative tumor volume was 16.4 cm3. Cavernous sinus invasion was present in 20 patients (52.63%). A gross-total resection was possible in 9 (23.68%) patients. The entire cohort’s mean absolute tumor stiffness value was 1.8 kPa (range 1.1–3.7 kPa), whereas the mean tumor stiffness ratio was 0.66 (range 0.37–1.6). Intraoperative tumor consistency was significantly correlated with absolute and relative tumor stiffness (p = 0.0087 and 0.007, respectively). Tumor consistency alone was not a significant factor for predicting gross-total resection. Patients with intermediate and firm tumors had more complications compared to patients with soft tumors (50.00% vs 12.50%, p = 0.02) and also had longer operative times (p = 0.0002). CONCLUSIONS Whereas other MRI sequences have proven to be unreliable in determining tumor consistency, MRE has been shown to be a reliable tool for predicting adenoma consistency. Preoperative knowledge of tumor consistency could be potentially useful for surgical planning, counseling about potential surgical risks, and estimating the length of operative time.


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Pinar Kadioglu ◽  
Emre Durcan ◽  
Fatma Ela Keskin ◽  
Hande Mefkure Ozkaya ◽  
Sabri Sirolu ◽  
...  

Abstract Biomarkers predicting tumor aggressiveness in pituitary adenomas have been largely investigated, albeit, with inconsistent results. We investigated the relationship of Fibroblast Growth Factor Receptor-4 (FGFR-4) expression and determined its relationship with radiological, pathological, and clinical parameters. In our study, 650 patients who were followed up for pituitary disease were reviewed from medical charts retrospectively. Of the 307 patients who underwent pituitary surgery for a pituitary adenoma between 2000 and 2015, we selected 161 cases on the basis of availability of pathology specimen of hypophysis tissue in our center. Patients’ radiological, pathological, and clinical parameters were obtained from medical charts. FGFR-4 immunostaining was evaluated using a semiquantitative Histologic score (H score). The mean age of the patients was 56.02 ± 14.80 years. Ninety-two (57.1%) were male and 69 (42.9%) were female. The mean follow-up period was 68.94 ± 44.15 months. Pathological examination revealed the following subtypes; 53 nonfunctioning pituitary adenomas, 26 corticotroph adenomas, 25 hormone receptor negative adenomas, 22 mammotroph adenomas, 13 somatotroph adenomas, 8 combined hormone secreting adenomas, 7 somatomammotroph, and 7 PIT-1 positive adenomas. The mean tumor size was 26.83 ± 14.92 mm. In patients with cavernous sinus invasion, the mean adenoma size was significantly higher than those without (p &lt;0.001). Mean H-score and Ki-67 levels were not different between patients with and without cavernous sinus invasion (p&gt;0.05 for all). The mean H-score, Ki-67, and adenoma size were significantly higher in patients without remission than those with remission (p &lt;0.001, p = 0.014, p &lt;0.001, respectively). The mean H score and adenoma size were significantly higher in patients with residual lesions than those without (p = 0.002, p &lt;0.001; respectively); there was no significant difference in Ki- 67 levels (p&gt;0.05). When the H-score and Ki-67 levels were assessed in terms of gender, sellar-dural invasion, tumor function or presence of poor subtype, no significant difference was detected (p&gt;0.05 for all). The mean H score and adenoma size were significantly higher in patients with Ki-67≥ 3 than those with &lt;3 (p = 0.002, p = 0.004; respectively). There was a weak positive correlation between H-score and Ki-67 (p = 0.005; r = 0.218); on the other hand, Ki-67 was not correlated with mitosis grade, p53 staining, and age, respectively (p&gt;0.05 for all). In our study, we demonstrated that patients with residual lesion and those without remission had high expression of FGFR-4. Also FGFR-4 levels were positively correlated with Ki-67 which itself correlated with lack of remission. Taken together, our results indicate that higher levels of FGFR-4 and Ki-67 in pituitary adenomas might indicate a more aggressive tumor phenotype.


Neurosurgery ◽  
2008 ◽  
Vol 62 (3) ◽  
pp. 717-723 ◽  
Author(s):  
Alvaro Campero ◽  
Carolina Martins ◽  
Alexandre Yasuda ◽  
Albert L. Rhoton

Abstract OBJECTIVE To evaluate the anatomic aspects of the diaphragma sellae and its potential role in directing the growth of a pituitary adenoma. METHODS Twenty cadaveric heads were dissected and measurements were taken at the level of the diaphragma sellae. RESULTS The diaphragma sellae is composed of two layers of dura mater. There is a remarkable variation in the morphology of the diaphragm opening. The average anteroposterior distance of the opening was 7.26 mm (range, 3.4–10.7 mm) and the average lateral-to-lateral distance was 7.33 mm (range, 2.8–14.1 mm). CONCLUSION The variability in the diameter of the opening of the diaphragma sellae could explain the growth of pituitary tumors toward the cavernous sinus or toward the suprasellar region.


2013 ◽  
Vol 149 (2_suppl) ◽  
pp. P48-P48
Author(s):  
Fabio Ferreli ◽  
Mario Turri-Zanoni ◽  
Stefania Gallo ◽  
Maurizio Bignami ◽  
Giustino Tomei ◽  
...  

2020 ◽  
Author(s):  
Guner Cakmak ◽  
Baris Mantoglu ◽  
Emre Gonullu ◽  
Kayhan Ozdemir ◽  
Burak Kamburoglu

Abstract Background: The objective of this study was to retrospectively compare clinical features and prognostic values between the patients who were referred to the general surgery clinic of our hospital with the presumed diagnosis of acute appendicitis and underwent positive or negative appendectomy.Methods: Patients were divided into two groups as positive (PA) (n:362) and negative appendectomy (NA) (n:284) and the data obtained were compared between these two groups.Laboratory investigations were performed in all patients, and white blood cell (WBC), mean platelet volume (MPV), neutrophils count (NEU), neutrophils (%) (NEU%), C-reactive protein (CRP) and total bilirubin (TBIL) values were studied.Results: The mean MPV value was found as 7.88 fl in PA groups and 8.09 fl in NA group, and the mean MPV value was not statistically significantly difference in PA group, compared to NA groups (p=0.012). Laboratory parameters were also compared between genders. Accordingly, the mean MPV value was statistically significantly higher in female patients compared to male patients in PA group (p = 0.04). The mean TBIL value was 0.97 mg/dl in PA group and 0.69 mg/dl in NA group, and the mean TBIL value was statistically significantly higher in PA group (p< 0.001). Finally, TBIL value was statistically significantly lower in female patients compared to male patients in NA and PA group (p < 0.05).Conclusions: According to the results of our study, MPV and T. BIL values differ in PA and NA groups depending on gender. Therefore, these values may not be used as specific biomarkers in predicting positive acute appendicitis. We believe that these results will contribute to the literature and will be guiding for future studies.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Maryam Dehghani ◽  
Zahra Davoodi ◽  
Farahnaz Bidari ◽  
Amin Momeni Moghaddam ◽  
Davood Khalili ◽  
...  

Abstract Background Regarding the inconclusive results of previous investigations, this study aimed to determine the association between pathology, as a possible predictor, with remission outcomes, to know the role of pathology in the personalized decision making in acromegaly patients. Methods A retrospective cohort study was performed on the consecutive surgeries for growth hormone (GH) producing pituitary adenomas from February 2015 to January 2021. Seventy-one patients were assessed for granulation patterns and prolactin co-expression as dual staining adenomas. The role of pathology and some other predictors on surgical remission was evaluated using logistic regression models. Results Among 71 included patients, 34 (47.9%) patients had densely granulated (DG), 14 (19.7%) had sparsely granulated (SG), 23 (32.4%) had dual staining pituitary adenomas. The remission rate was about 62.5% in the patients with SG and DG adenomas named single staining and 52.2% in dual staining groups. Postoperative remission was 1.53-folds higher in the single staining adenomas than dual staining-one (non-significant). The remission rate was doubled in DG group compared to two other groups (non-significant). By adjusting different predictors, cavernous sinus invasion and one-day postoperative GH levels decreased remission rate by 91% (95% CI: 0.01–0.67; p = 0.015) and 64% (95% CI: 0.19–0.69; p < 0.001), respectively. Responses to the medications were not significantly different among three groups. Conclusion Various pathological subtypes of pituitary adenomas do not appear to have a predictive role in estimating remission outcomes. Cavernous sinus invasion followed by one-day postoperative GH is the strongest parameter to predict biochemical remission.


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