scholarly journals How Valuable Is the RT-qPCR of Pituitary-Specific Transcription Factors for Identifying Pituitary Neuroendocrine Tumor Subtypes According to the New WHO 2017 Criteria?

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1990 ◽  
Author(s):  
María Eugenia Torregrosa-Quesada ◽  
Araceli García-Martínez ◽  
Sandra Silva-Ortega ◽  
Sebastián Martínez-López ◽  
Rosa Cámara ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Pituitary Tumors ◽  
World Health ◽  
Null Cell ◽  
Tumor Subtypes ◽  
Esr1 Gene ◽  
Gene And Protein Expression ◽  
Health Organization ◽  
Immunohistochemical Studies

The classification of pituitary neuroendocrine tumors (PitNETs) subtypes continues generating interest. In 2017, the World Health Organization (WHO) proposed considering the immunohistochemical (IHC) analysis of pituitary-specific transcription factors (TF) for their typification. The present study targeted the quantification of pituitary-specific TF (TPIT, PIT-1, SF-1, GATA2, ESR1) gene expression by RT-qPCR to overcome the shortcomings of IHC and to complement it. We analyzed 251 tumors from our collection of PitNETs and performed additional IHC studies in a subset of 56 samples to analyze the concordance between gene and protein expression of the TF. The molecular and IHC studies allowed us to significantly reduce the percentage of null cell tumors in our series, most of which were reclassified as gonadotroph tumors. The concordance between the molecular and the immunohistochemical studies was good for tumors coming from the corticotroph and Pit-1 lineages but worsened for the rest of the tumors. Indeed, the RT-qPCR helped to improve the typification of plurihormonal Pit-1 and unusual tumors. Overall, our results suggest that the RT-qPCR of pituitary-specific TF and hormone genes could help pathologists, endocrinologists, and neurosurgeons to improve the management of patients with pituitary tumors.

scholarly journals Pathohistological classification of pituitary tumors: 10 years of experience with the German Pituitary Tumor Registry

2007 ◽  
Vol 156 (2) ◽  
pp. 203-216 ◽  
Author(s):  
Wolfgang Saeger ◽  
Dieter K Lüdecke ◽  
Michael Buchfelder ◽  
Rudolf Fahlbusch ◽  
Hans-Jürgen Quabbe ◽  
...  
Keyword(s):  
Pituitary Tumors ◽  
German Society ◽  
World Health ◽  
Null Cell ◽  
Cell Adenoma ◽  
Tumor Registry ◽  
Acth Cell ◽  
Oncocytic Variant ◽  
Health Organization

In 1996, the German Registry of Pituitary Tumors was founded by the Pituitary Section of the German Society of Endocrinology as a reference center for collection and consultant pathohistological studies of pituitary tumors. The experiences of the first 10 years of this registry based on 4122 cases will herein be reported. The data supplement former collections of the years 1970–1995 with 3480 surgically removed tumors or lesions of the pituitary region. The cases were studied using histology, immunostainings and in some cases also molecular pathology or electron microscopy. The adenomas were classified according to the current World Health Organization classification in the version of 2004. From 1996 on 3489 adenomas (84.6%), 5 pituitary carcinomas (0.12%), 133 craniophar-yngiomas (3.2%), 39 meningiomas (0.94%), 25 metastases (0.6%), 22 chordomas (0.5%), 115 cystic non-neoplastic lesions (2.8%), and 46 inflammatory lesions (1.1%, 248 other lesions or normal tissue (6.0%)) were collected by us. The adenomas (100%) were classified into densely granulated GH cell adenomas (9.2%), sparsely granulated GH cell adenomas (6.3%), sparsely granulated prolactin (PRL) cell adenomas (8.9%), densely granulated PRL cell adenomas (0.3%), mixed GH/PRL cell adenomas (5.2%), mammosomatotropic adenomas (1.1%), acidophilic stem cell adenomas (0.2%), densely granulated ACTH cell adenomas (7.2%), sparsely granulated ACTH cell adenomas (7.9%), Crooke cell adenomas (0.03%), TSH cell adenomas (1.5%), FSH/LH cell adenomas (24.8%), null cell adenomas (19.3%), null cell adenoma, oncocytic variant (5.8%), and plurihormonal adenomas (1.3%). Following the WHO classification of 2004, the new entity ‘atypical adenoma’ was found in 12 cases in 2005. Various prognostic parameters and clinical implications are discussed.

scholarly journals SUN-135 Characterization of Transcription Factor Immunostaining and Null Cell Adenoma Status in Hormone Negative Pituitary Adenomas

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Hans C Baertsch ◽  
Dhiraj J Pangal ◽  
Trey Garrett ◽  
Andrew Brunswick ◽  
Martin Rutkowski ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Pituitary Adenomas ◽  
Vision Loss ◽  
World Health ◽  
Tumor Diameter ◽  
Null Cell ◽  
Cell Adenoma ◽  
Cavernous Sinus Invasion ◽  
Endocrine Organs

Abstract Introduction: Since the 2017 W.H.O. classification of pituitary adenomas redefined null cell adenomas (NCAs) as negative for all adenohypophyseal hormones and the transcription factors (TFs) SF-1, PIT-1, and T-PIT, limited data exist characterizing these tumors1. We characterize NCAs in comparison to hormone negative adenomas (HNAs), which demonstrate negative hormone immunostaining in the context of positive TF immunoreactivity. Methods: Retrospective review of 22 patients with HNAs between 2011-2019. Samples were stained for PIT-1 and SF-1. Negative ACTH staining served as a proxy for T-PIT given demonstrated prior concordance of these stains2. Demographics, tumor characteristics, preoperative symptoms, and postoperative outcomes were assessed. Results: Fifteen samples (68%) stained negative for both PIT-1 and SF-1 and were classified as NCAs. Seven were positive for SF-1 (n=3), PIT-1 (n=3), or both (n=1) and were classified as HNAs. NCA patients were predominantly female (80%), while those with HNAs were predominantly male (57%). All tumors were macroadenomas, with mean maximal tumor diameter of 28mm in NCAs vs 23mm in HNAs (p=0.2705). NCAs were more likely to demonstrate suprasellar invasion (100% vs. 71%, p=0.0325), and although not statistically significant, cavernous sinus invasion (53% vs. 43%, p=0.6695), and higher MIB-1 proliferative index (2.271 vs. 1.971, p=0.733). The most common preoperative symptoms were headache (73% NCA, 71% HNA) and vision loss (53%, 40%). Postoperative improvements in headache (60% NCA, 71% HNA) and vision (53%, 50%) were comparable. Sixty-four percent of NCAs underwent gross total resection vs. 43% of HNAs (p=.3712). There were no recurrences or progressions in either group over 24mo. Few comparisons reached significance, potentially due to limited sample size. Conclusion: A majority of HNAs demonstrated negative TF immunostaining and met criteria for NCAs. NCAs may be more common in females and demonstrate more suprasellar invasion than HNAs, but otherwise, do not vary significantly. TF staining may be of limited clinical utility in identifying high-risk pathology, however future studies with larger cohorts are warranted. References: 1. Osamura RY, Lopes MBS, Grossman A, Matsuno A, Korbonits M, Trouillas J, Kovacs K (2017) Pituitary adenoma. In: Lloyd RV, Osamura RY, Klöppel G, Rosai J (eds) World health organization classification of tumours of endocrine organs, 4th edn. IARC, Lyon, pp 14-18. 2. Nishioka H, Inoshita N, Mete O, Asa SL, Hayashi K, Takeshita A, Fukuhara N, Yamaguchi-Okadad M, Takeuchi Y, Yamada S (2015) The Complementary Role of Transcription Factors in the Accurate Diagnosis of Clinically Nonfunctioning Pituitary Adenomas. Endocr Path 26(4):249-55.

scholarly journals Inter-Observer Variation in the Grading of Meningiomas using the WHO Classification of CNS Tumors Criteria

2020 ◽  
pp. 1-5
Author(s):  
Hisham Alkhalidi
Keyword(s):  
Who Classification ◽  
Observer Variation ◽  
World Health ◽  
Original Diagnosis ◽  
Brain Invasion ◽  
Tumor Subtypes ◽  
The Central Nervous System ◽  
Health Organization ◽  
Treatment Prognosis

Background: Grading of meningiomas using the World health organization (WHO) Classification of the Central Nervous System criteria currently has an essential role in classification, treatment, prognosis prediction, and research of these tumors. Aims: This is a retrospective study that assessed the interobserver variation between Anatomical Pathologists in grading meningiomas using material obtained from ten resection specimens. The WHO grading system includes different methods, including the mitotic count, the tumor subtypes or the presence of three out of five certain morphological features. This paper focuses on the interobserver variability in the latter method. Methods: Meningiomas that were originally graded based upon mitoses, brain invasion, or morphological subtype were excluded. Ten different Anatomical Pathologists, including two Neuropathologists, who were blinded to the original diagnosis and grade graded the tumors independently.

Variability and Lack of Prognostic Value Associated With Atypical Pituitary Adenoma Diagnosis: A Systematic Review and Critical Assessment of the Diagnostic Criteria

Neurosurgery ◽  
2017 ◽  
Vol 83 (4) ◽  
pp. 602-610 ◽  
Author(s):  
Kelsi Chesney ◽  
Zoe Memel ◽  
Dhiraj J Pangal ◽  
Daniel Donoho ◽  
Kyle Hurth ◽  
...  
Keyword(s):  
Systematic Review ◽  
Pituitary Adenomas ◽  
Pituitary Tumors ◽  
World Health ◽  
Resonance Imaging ◽  
Prognostic Utility ◽  
Atypical Pituitary Adenoma ◽  
Health Organization

Abstract BACKGROUND Atypical pituitary adenomas (APAs) are a subset of pituitary adenomas (PAs) characterized by the 2004 World Health Organization (WHO) guidelines to have higher risk histopathological features than typical PAs. In July 2017, the WHO published an update to their classification of pituitary tumors and abandoned the APA terminology. OBJECTIVE To assess the prevalence and outcomes of patients diagnosed with APA through a literature review. Focus was placed on variation in the application of the previous WHO criteria and on rates of recurrence. METHODS A systematic review of PubMed (2004-July 2017) was performed to identify studies reporting prevalence and clinical characteristics/outcomes of APA. Eight studies were analyzed for prevalence. Six studies reporting histopathological details were analyzed in depth. RESULTS Of the 7105 included patients, 373 (5.2%) met criteria for APA (prevalence range: 3%-15%). Only 2 of 8 studies utilized identical grading criteria, demonstrating a lack of standardized application. Most APAs (84%) were macroadenomas, with 52% invasive on magnetic resonance imaging. Nonfunctional PAs were most common (37%), followed by prolactinomas (23%) and Growth Hormone adenomas (21%). Recurrence/progression occurred in 21% of APA patients (follow-up range 37-75 mo). Only 2 of 8 studies reported an association between APA diagnosis and recurrence/progression. CONCLUSION Based on diagnostic variability and lack of association with clinical outcomes, refinement of criteria for APA was necessary. The WHO update eliminates the ambiguity in APA diagnosis in favor of criteria that emphasize clinical behavior (invasion, recurrence, and resistance to treatment) and molecular markers. Our review supports abandonment of the previous APA designation due to limited prognostic utility.

Clinical Implications of the New WHO Classification 2017 for Pituitary Tumors

2021 ◽  
Vol 129 (03) ◽  
pp. 146-156 ◽  
Author(s):  
Wolfgang Saeger ◽  
Arend Koch
Keyword(s):  
Transcription Factors ◽  
Who Classification ◽  
Cell Lineage ◽  
Pituitary Tumors ◽  
Pituitary Hormones ◽  
Null Cell ◽  
Cell Adenoma ◽  
Ki 67 ◽  
Worse Prognosis

AbstractAccording to the WHO classification 2017 of Pituitary Tumors adenomas are classified not only by structure and immunostaining for pituitary hormones but also by expression of the pituitary transcription factors Pit-1, T-pit and SF-1. By these factors, three cell lineages can be identified: Pit-1 for the GH-, Prolactin- and TSH-cell lineage, T-pit for the ACTH-cell lineage, and SF-1 for the gonadotrophic cell lineage. By this principle, all GH and/or Prolactin producing and all TSH producing adenomas must be positive for Pit-1, all corticotrophic adenomas for T-pit, and all gonadotrophic for SF-1. In adenomas without expression of pituitary hormones immunostainings for the transcription factors have to be examined. If these are also negative the criteria for an endocrine inactive null cell adenoma are fulfilled. If one transcription factor is positive the corresponding cell lineage indicates a potential hormonal activity of the adenoma. So Pit-1 expressing hormone-negative adenomas can account for acromegaly, hyperprolactinemia, or TSH hyperfunction. T-pit positive hormone negative adenomas can induce Cushing’s disease, and SF-1 positive hormone negative tumors indicate gonadotrophic adenomas. Instead of the deleted atypical adenoma of the WHO classification of 2004 now (WHO classification 2017) criteria exist for the identification of aggressive adenomas with a conceivably worse prognosis. Some adenoma subtypes are described as aggressive “per se” without necessity of increased morphological signs of proliferation. All other adenoma subtypes must also be designated as aggressive if they show signs of increased proliferation (mitoses, Ki-67 index>3–5%, clinically rapid tumor growth) and invasion. By these criteria about one third of pituitary adenoma belong to the group of aggressive adenomas with potentially worse prognosis. The very rare pituitary carcinoma (0.1 % of pituitary tumors) is defined only by metastases. Many of them develop after several recurrences of Prolactin or ACTH secreting adenomas. The correlation of clinical findings and histological classification of pituitary adenomas is very important since every discrepancy has to be discussed between clinicians and pathologists. Based on data of the German Registry of Pituitary Tumors a table for examinations of correlations is shown in this review.

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