The immunohistochemical and radiological features of nonfunctioning pituitary adenomas

2015 ◽  
Vol 61 (6) ◽  
pp. 4-9 ◽  
Author(s):  
Anna Konstantinovna Lipatenkova ◽  
Larisa Konstantinovna Dzeranova ◽  
Ekaterina Aleksandrovna Pigarova ◽  
Nadezhda Sergeevna Dalantaeva ◽  
Ljudmila Igorevna Astaf'eva ◽  
...  
Keyword(s):  
Pituitary Adenomas ◽  
Area Under The Curve ◽  
Pituitary Hormones ◽  
Serum Markers ◽  
Invasive Growth ◽  
Null Cell ◽  
Ki 67 ◽  
Nonfunctioning Pituitary Adenomas ◽  
Radiological Features ◽  
Null Cell Adenomas

Pituitary adenomas without clinically active hypersecretion are summarized under the term nonfunctioning pituitary adenomas (NFPAs). Since there are no specific serum markers, the differential diagnosis and treatment imply special difficulties.Aim.To investigate the immunohistochemical and radiological features of NFPAs and assess the granins — chromogranin A (CgA), secretogranin II (SgII), secretoneurin (Sn) as immunohistochemical markers of NFPAs.Matherial and methods.50 pituitary adenomas excised surgically were immunostained to reveal pituitary hormones, ki-67, CgА. SgII, Sn. All patients underwent MRI, invasive growth was estimated due to J.Hardy classification (1973).Results.24 (51,1%) were gonadotropic tumors, 12 (25,5%) — null cell adenomas. Immunopositivity for ACTH was determined in 6 cases (12,7%), for GH in 5 (10,6%) cases, for PRL in 4 (8,5%). The median level of ki-67 was 2% (min. — 0.5%, max. — 7%). The CgA, SgII, Sn immunopositivity was found in 83, 93,6, 85,1% respectively, being more expressed in gonadotropinomas and null cell adenomas. Invasive growth was detected in 28 (44%) cases, among the invasive adenomas 22 tumors were giant. CgA expression is adverse prognostic factor, area under the curve (AUC) with 0,705. We did not find any correlation between ACTH-, STH-, CgII- and Sn- immunopositivity, ki-67 and invasive growth.Conclusions.Our work shows that a majority of NFPAs are truly secreting adenomas with significant numbers comprising potentially hazardous cortico- and somatotropinomas. CgA, SgII and Sn have a high expression in most of the NFPAs.

Long-term results in transsphenoidal removal of nonfunctioning pituitary adenomas

1986 ◽  
Vol 64 (5) ◽  
pp. 713-719 ◽  
Author(s):  
Michael J. Ebersold ◽  
Lynn M. Quast ◽  
Edward R. Laws ◽  
Berndt Scheithauer ◽  
Raymond V. Randall
Keyword(s):  
Pituitary Adenomas ◽  
Mass Effect ◽  
Pituitary Hormones ◽  
Long Term Results ◽  
Null Cell ◽  
Content Type ◽  
Nonfunctioning Pituitary Adenomas ◽  
Presenting Symptoms

✓ Little has been written about the long-term results of transsphenoidal treatment for clinically nonfunctioning pituitary adenomas. The records of 100 patients who had undergone a transsphenoidal procedure for excision of such tumors were reviewed. Immunocytology for pituitary hormones was performed in all cases. The group consisted predominantly of null-cell adenomas, although a small number of prolactinomas and gonadotropic tumors were found. The mean diameter of the tumors at the time of detection was slightly more than 2 cm. In most cases, the presenting symptoms were due to the mass effect of the tumor (that is, visual symptoms in 72 patients, hypopituitarism in 61, headache in 36, and cranial nerve disturbance other than visual loss in 10). Radiation therapy was recommended for patients in whom subtotal removal of the adenoma was expected. Six patients developed symptomatic tumor recurrence, and 10 patients demonstrated radiographic recurrence during the 48 to 100 months (mean 73.4 months) of follow-up observation. Only three of 10 deaths during the follow-up period were due to pituitary disease or treatment.

Residual nonfunctioning pituitary adenomas: prognostic value of MIB-1 labeling index for tumor progression

2009 ◽  
Vol 111 (3) ◽  
pp. 563-571 ◽  
Author(s):  
Georg Widhalm ◽  
Stefan Wolfsberger ◽  
Matthias Preusser ◽  
Ingeborg Fischer ◽  
Adelheid Woehrer ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Pituitary Adenomas ◽  
Residual Tumor ◽  
Labeling Index ◽  
Ki 67 ◽  
Nonfunctioning Pituitary Adenomas ◽  
Time Period ◽  
Tumor Group ◽  
Significant Difference ◽  
Mib 1

Object In residual nonfunctioning pituitary adenomas, reliable prognostic parameters indicating probability of tumor progression are needed. The Ki 67 expression/MIB-1 labeling index (LI) is considered to be a promising candidate factor. The aim in the present study was to analyze the clinical usefulness of MIB-1 LI for prognosis of tumor progression. Methods The authors studied a cohort of 92 patients with nonfunctioning pituitary adenomas. Based on sequential postoperative MR images, patients were classified as tumor free (51 patients) or as harboring residual tumor (41 individuals). The residual tumor group was further subdivided in groups with stable residual tumors (14 patients) or progressive residual tumors (27 patients). The MIB-1 LI was assessed in tumor specimens obtained in all patients, and statistical comparisons of MIB-1 LI of the various subgroups were performed. Results . The authors found no significant difference of MIB-1 LI in the residual tumor group compared with the tumor-free group. However, MIB-1 LI was significantly higher in the progressive residual tumor group, compared with the stable residual tumor group. Additionally, the time period to second surgery was significantly shorter in residual adenomas showing an MIB-1 LI > 3%. Conclusions The data indicate that MIB-1 LI in nonfunctioning pituitary adenomas is a clinically useful prognostic parameter indicating probability of progression of postoperative tumor remnants. The MIB-1 LI may be helpful in decisions of postoperative disease management (for example, frequency of radiographic intervals, planning for reoperation, radiotherapy, and/or radiosurgery).

Expression of Ki-67 antigen in nonfunctioning pituitary adenomas: correlation with growth velocity and invasiveness

2003 ◽  
Vol 99 (4) ◽  
pp. 674-679 ◽  
Author(s):  
Jürgen Honegger ◽  
Carsten Prettin ◽  
Friedrich Feuerhake ◽  
Manfred Petrick ◽  
Jürgen Schulte-Mönting ◽  
...  
Keyword(s):  
Growth Rate ◽  
Growth Velocity ◽  
Pituitary Adenomas ◽  
Growth Potential ◽  
Nuclear Antigen ◽  
Ki 67 ◽  
Content Type ◽  
Nonfunctioning Pituitary Adenomas ◽  
Invasive Behavior ◽  
Fine Print

Object. The cell cycle—dependent nuclear antigen Ki-67 is related to growth potential in a variety of tumors. Elevated expression of Ki-67 was previously shown in recurrent pituitary adenomas; however, it has remained unclear whether this expression is related to the growth velocity or invasive behavior of these tumors. The aim of this study was to determine the correlation of Ki-67 antigen expression, growth velocity, and invasiveness in nonfunctioning pituitary adenomas. Methods. Between April 1998 and April 2002, 23 patients with nonfunctioning pituitary adenomas who had participated in an observation period in which multiple computerized tomography and magnetic resonance imaging studies had been performed were surgically treated in our department. Tumor volumes were assessed using a stereological method based on the Cavalieri principle. The growth rate was calculated for each patient. Expression of Ki-67 antigen was examined using the monoclonal antibody MIB-1. The assessed growth velocity of the adenomas was best described by a linear growth model. The correlation between Ki-67 expression and growth rate was highly significant. Rapidly growing adenomas (>0.07% daily increase in size) were found to have a Ki-67 labeling index (LI) exceeding 1.5%, whereas all five adenomas with a very slow growth rate (< 0.02% daily increase in size) had a Ki-67 LI lower than 1.5%. No correlation was found between the growth rate and the invasive character of the adenomas. Conclusions. Expression of Ki-67 antigen is significantly correlated to the growth velocity of pituitary adenomas. Invasive behavior is a feature independent of proliferative activity. The extent of Ki-67 expression is helpful for clinical decision making and routine assessment of Ki-67 is recommended during the histopathological workup of pituitary adenomas.

Proliferation Index of Nonfunctioning Pituitary Adenomas: Correlations with Clinical Characteristics and Long-term Follow-up Results

Neurosurgery ◽  
2000 ◽  
Vol 47 (6) ◽  
pp. 1313-1319 ◽  
Author(s):  
Marco Losa ◽  
Alberto Franzin ◽  
Francesca Mangili ◽  
Maria Rosa Terreni ◽  
Raffaella Barzaghi ◽  
...  
Keyword(s):  
Pituitary Adenomas ◽  
Tumor Recurrence ◽  
Clinical Characteristics ◽  
Ki 67 ◽  
Nonfunctioning Pituitary Adenomas ◽  
Age At Surgery ◽  
Long Term Follow Up ◽  
The Mean

ABSTRACT OBJECTIVE The recurrence of nonfunctioning pituitary adenomas (NFPAs) after surgical removal is common. The aim of our study was to investigate and correlate the growth fraction of NFPAs with clinical characteristics and long-term follow-up results. METHODS Tumor specimens were obtained from 101 consecutive patients with NFPAs (48 female patients and 53 male patients; mean age, 52.0 ± 1.5 yr). Specimens were immediately fixed in 10% buffered formalin and then embedded in paraffin. The Ki-67 antigen was assessed by immunocytochemical analysis using the monoclonal antibody MIB-1. The Ki-67 antigen labeling index (LI) was determined by counting a total of at least 1000 neoplastic nuclei. RESULTS The mean Ki-67 LI for the 101 patients was 2.4 ± 0.3% (range, 0–23.0%). Only age at surgery was inversely correlated with the Ki-67 LI; sex, maximal tumor diameter, and invasiveness into the cavernous sinuses did not significantly affect the Ki-67 LI. The mean follow-up period was 39.7 ± 2.1 months. During follow-up monitoring, 23 patients experienced tumor recurrence, after a mean period of 28.6 ± 4.8 months. Invasiveness of the tumor on preoperative magnetic resonance imaging scans was the strongest predictor of late tumor recurrence, followed by previous pituitary surgery, younger age, and lack of postoperative radiotherapy. The Ki-67 LI had no independent prognostic value. CONCLUSION Our study suggests that the clinical characteristics of patients with NFPAs, except for age at surgery, are not correlated with the Ki-67 LI. Moreover, the Ki-67 LI does not seem to provide independent information to identify patients at high risk for tumor recurrence.

Morphological study of clinically nonsecreting pituitary adenomas in patients under 40 years of age

1991 ◽  
Vol 75 (6) ◽  
pp. 902-905 ◽  
Author(s):  
Shozo Yamada ◽  
Kalman Kovacs ◽  
Eva Horvath ◽  
Tadashi Aiba
Keyword(s):  
Microscopic Examination ◽  
Pituitary Adenomas ◽  
Electron Microscopic Examination ◽  
Electron Microscopic ◽  
Null Cell ◽  
Younger Patients ◽  
Content Type ◽  
Morphological Studies ◽  
Null Cell Adenomas ◽  
Fine Print

✓ Clinically nonsecreting pituitary adenomas removed at surgery from 69 patients under 40 years of age were studied by histological, immunocytochemical, and transmission electron microscopic examination. By morphological analysis. 19 tumors were found to be null-cell adenomas. 17 silent gonadotroph adenomas, 14 silent subtype 3 adenomas of unknown cellular origin, 13 silent subtype 1 or subtype 2 corticotroph adenomas, three oncocytomas, and three silent thyrotroph adenomas. These results indicate that the incidence of null-cell adenomas and oncocytomas, which are known to be the most common types of nonsecreting pituitary adenomas in patients over 40 years of age, is relatively low in younger patients. This trend is even more obvious in patients younger than 30 years of age. It can be concluded that clinically nonsecreting pituitary adenomas represent a heterogeneous group morphologically, and that the incidence of the different tumor types varies depending on the patient's age. These findings underline the importance of careful morphological studies. It is proposed that, in order for the correct morphological diagnosis to be made, tumors removed surgically from patients with clinically nonsecreting pituitary adenomas (especially younger patients) should be investigated not only by histological means but also by immunocytochemical and electron microscopic examination. The information obtained from such analysis may be useful in assessing prognosis and deciding on the appropriate treatment.

Utility of Pit-1 Immunostaining in Distinguishing Pituitary Adenomas of Primitive Differentiation from Null Cell Adenomas

2017 ◽  
Vol 28 (4) ◽  
pp. 287-292 ◽  
Author(s):  
Julieann C. Lee ◽  
Melike Pekmezci ◽  
Jonathan L. Lavezo ◽  
Hannes Vogel ◽  
Laurence Katznelson ◽  
...  
Keyword(s):  
Pituitary Adenomas ◽  
Null Cell ◽  
Null Cell Adenomas

scholarly journals Comprehensive Analysis of Circulating miRNAs in the Plasma of Patients With Pituitary Adenomas

2019 ◽  
Vol 104 (9) ◽  
pp. 4151-4168 ◽  
Author(s):  
Kinga Németh ◽  
Ottó Darvasi ◽  
István Likó ◽  
Nikolette Szücs ◽  
Sándor Czirják ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Pituitary Adenomas ◽  
Tumor Recurrence ◽  
Area Under The Curve ◽  
Improve Patient Care ◽  
Extracellular Vesicle ◽  
Pituitary Hormones ◽  
Plasma Samples ◽  
Circulating Mirnas ◽  
Altered Expression

Abstract Background Circulating miRNAs in pituitary adenomas would improve patient care, especially as minimally invasive biomarkers of tumor recurrence and progression in nonfunctioning adenoma cases. Aim Our aim was to investigate plasma miRNA profiles in patients with pituitary adenomas. Materials and Methods A total of 149 plasma and extracellular vesicle (preoperative, early postoperative, and late postoperative) samples were collected from 45 patients with pituitary adenomas. Adenomas were characterized on the basis of anterior pituitary hormones and transcription factors by immunostaining. miRNA next-generation sequencing was performed on 36 samples (discovery set). Individual TaqMan assays were used for validation on an extended sample set. Pituitary adenoma tissue miRNAs were evaluated by TaqMan array and data in the literature. Results Global downregulation of miRNA expression was observed in plasma samples of pituitary adenomas compared with normal samples. Expression of 29 miRNAs and isomiR variants were able to distinguish preoperative plasma samples from normal controls. miRNAs with altered expression in both plasma and different adenoma tissues were identified. Three, seven, and 66 miRNAs expressed differentially between preoperative and postoperative plasma samples in GH-secreting, FSH/LH+, and hormone-immunonegative groups, respectively. miR‒143-3p was downregulated in late postoperative but not in early postoperative plasma samples compared with preoperative ones exclusively in FSH/LH+ adenomas. The plasma level of miR‒143-3p discriminated these samples with 81.8% sensitivity and 72.3% specificity (area under the curve = 0.79; P = 0.02). Conclusions Differentially expressed miRNAs in pituitary adenoma tissues have low abundance in plasma, minimizing their role as biomarkers. Plasma miR‒143-3p level decreased in patients with FSH/LH+ adenomas, indicating successful surgery, but its application for evaluating tumor recurrence needs further investigation.

Are Nonfunctioning Pituitary Adenomas Extending into the Cavernous Sinus Aggressive and/or Invasive?

Neurosurgery ◽  
2001 ◽  
Vol 49 (4) ◽  
pp. 857-863 ◽  
Author(s):  
Shunichi Yokoyama ◽  
Hirofumi Hirano ◽  
Koichi Moroki ◽  
Masamichi Goto ◽  
Shinichi Imamura ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Cavernous Sinus ◽  
Cathepsin B ◽  
Pituitary Adenomas ◽  
Control Group ◽  
Resonance Imaging ◽  
Ki 67 ◽  
Nonfunctioning Pituitary Adenomas ◽  
Extension Group

Abstract OBJECTIVE We studied nonfunctioning pituitary adenomas extending to the cavernous sinus to gain insight into the discrepancy between their histologically benign nature and frequent extension into the cavernous sinus. METHODS We studied 10 patients with nonfunctioning pituitary adenomas that completely encircled the cavernous carotid artery (extension group). All 10 patients underwent surgery to remove intrasellar and/or suprasellar parts of the adenomas. Ten patients with nonfunctioning pituitary adenomas without cavernous sinus extension comprised the control group. Tumor size follow-up data were obtained by magnetic resonance imaging. Immunostaining was performed for Ki-67, cathepsin B, and matrix metalloprotainase-9. To assess the wall thickness, 10 cavernous sinuses were removed from the cranial base of adult cadavers, and the walls were examined histologically. RESULTS Magnetic resonance imaging demonstrated no remarkable growth in most of the patients during the follow-up period (mean, 65.8 mo). There was no statistical difference in Ki-67, cathepsin B, and matrix metalloprotainase-9 immunostaining between the extension group and the control group. The cadaver study demonstrated that the medial wall was significantly thinner than the superior and the lateral walls (P &lt; 0.0005). We found small defects in the capsule histologically in 3 of 30 sections. CONCLUSION Our results indicate that most of nonfunctioning pituitary adenomas extending into the cavernous sinus are neither aggressive nor invasive. The high incidence of cavernous sinus extension of benign adenomas may be caused by the weakness of the medial wall of the cavernous sinus.

scholarly journals Somatotropinomas, But Not Nonfunctioning Pituitary Adenomas, Maintain a Functional Apoptotic RET/Pit1/ARF/p53 Pathway That Is Blocked by Excess GDNF

Endocrinology ◽  
2014 ◽  
Vol 155 (11) ◽  
pp. 4329-4340 ◽  
Author(s):  
Esther Diaz-Rodriguez ◽  
Angela R. Garcia-Rendueles ◽  
Alejandro Ibáñez-Costa ◽  
Ester Gutierrez-Pascual ◽  
Montserrat Garcia-Lavandeira ◽  
...  
Keyword(s):  
Pituitary Adenomas ◽  
Primary Cultures ◽  
Survival Function ◽  
Pituitary Hormones ◽  
Rt Pcr ◽  
Steroidogenic Factor 1 ◽  
Apoptosis Pathway ◽  
Nonfunctioning Pituitary Adenomas ◽  
Enhancer Binding Protein ◽  
In Silico Studies

Abstract Acromegaly is caused by somatotroph cell adenomas (somatotropinomas [ACROs]), which secrete GH. Human and rodent somatotroph cells express the RET receptor. In rodents, when normal somatotrophs are deprived of the RET ligand, GDNF (Glial Cell Derived Neurotrophic Factor), RET is processed intracellularly to induce overexpression of Pit1 [Transcription factor (gene : POUF1) essential for transcription of Pituitary hormones GH, PRL and TSHb], which in turn leads to p19Arf/p53-dependent apoptosis. Our purpose was to ascertain whether human ACROs maintain the RET/Pit1/p14ARF/p53/apoptosis pathway, relative to nonfunctioning pituitary adenomas (NFPAs). Apoptosis in the absence and presence of GDNF was studied in primary cultures of 8 ACROs and 3 NFPAs. Parallel protein extracts were analyzed for expression of RET, Pit1, p19Arf, p53, and phospho-Akt. When GDNF deprived, ACRO cells, but not NFPAs, presented marked level of apoptosis that was prevented in the presence of GDNF. Apoptosis was accompanied by RET processing, Pit1 accumulation, and p14ARF and p53 induction. GDNF prevented all these effects via activation of phospho-AKT. Overexpression of human Pit1 (hPit1) directly induced p19Arf/p53 and apoptosis in a pituitary cell line. Using in silico studies, 2 CCAAT/enhancer binding protein alpha (cEBPα) consensus-binding sites were found to be 100% conserved in mouse, rat, and hPit1 promoters. Deletion of 1 cEBPα site prevented the RET-induced increase in hPit1 promoter expression. TaqMan qRT-PCR (real time RT-PCR) for RET, Pit1, Arf, TP53, GDNF, steroidogenic factor 1, and GH was performed in RNA from whole ACRO and NFPA tumors. ACRO but not NFPA adenomas express RET and Pit1. GDNF expression in the tumors was positively correlated with RET and negatively correlated with p53. In conclusion, ACROs maintain an active RET/Pit1/p14Arf/p53/apoptosis pathway that is inhibited by GDNF. Disruption of GDNF's survival function might constitute a new therapeutic route in acromegaly.

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