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.

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 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.

Ultrastructural Classification of Pituary Adenomas

1990 ◽  
Vol 48 (3) ◽  
pp. 258-258
Author(s):  
S. Arumugam ◽  
Sarasa Bharati Arumugam
Keyword(s):  
Cytoplasmic Organelle ◽  
Null Cell ◽  
Cell Adenoma ◽  
Mixed Cell ◽  
Light Microscope Level ◽  
Null Cell Adenoma ◽  
Growth Hormone Cell ◽  
Ultrastructural Characteristics ◽  
Organelle Morphology

Adenoaas of the pituitary are no longer classified based on their tinctorial affinity to dyes. With the advent of the newer methods of sophisticated technology, it is now possible to classify. These depending upon the type of hormone secreted based either on histochemical techniques or on ultrastructural characteristics. The latter provides an insight into the cytoplasmic organelle morphology which offers a delightful feast to the eye as well.This paper presents the ultrastructural characters of the pituitary adenoma as seen in Madras. 171 adenomas (124 males and 47 females) were seen during 1972-1989, classified at the light microscope level as 159 chromophobe, 2 basophilic, 4 eosinophilic and 6 mixed adenomas.Ultrastructural examination showed that the sparsely granular prolactin cell adenoma is the commonest adenoma to be encountered closely followed by the growth hormone cell adenoma, null cell adenoma, the mixed cell adenoma and others.

The new WHO classification of human pituitary tumors: comments

2005 ◽  
Vol 111 (1) ◽  
pp. 71-72 ◽  
Author(s):  
Dominique Figarella-Branger ◽  
Jacqueline Trouillas
Keyword(s):  
Who Classification ◽  
Pituitary Tumors ◽  
Human Pituitary

Monocytosis As Prognostic Factor in Aggressive, Non-Primary Cutaneous Peripheral T-Cell Lymphoma: A Study of 251 Cases

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1608-1608
Author(s):  
Brady E Beltran ◽  
Erick Cotacallapa ◽  
Jorge J Castillo
Keyword(s):  
Overall Survival ◽  
T Cell ◽  
Who Classification ◽  
Cell Lymphoma ◽  
Statistical Significance ◽  
Prognostic Index ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma ◽  
Worse Prognosis

Abstract Abstract 1608 Background: Peripheral T-cell lymphoma (PTCL) is a heterogeneous family of entities with a worse prognosis, stage by stage, than their B-cell counterparts. We have previously reported that an absolute lymphocyte count (ALC) <1000/uL is associated with a worse prognosis in Peruvian patients with PTCL (Castillo et al. 2010). The goal of this study is to investigate the prognostic value of absolute monocyte count (AMC) in the survival of patients with PTCL. Methods: A total of 251 cases of aggressive, non-primary cutaneous PTCL diagnosed at our institution between January 1997 and January 2012 were reviewed, reevaluated according to their morphological, immunological and clinical characteristics, and reclassified according to the 2008 WHO classification of lymphoid neoplasms. Characteristics will be presented descriptively. Kaplan-Meier method was used to estimate overall survival (OS) curves, which were compared using the log-rank test. The multivariate analysis was performed using the Cox proportional-hazard regression test. Results: According to the new WHO classification of lymphoid neoplasms, 104 cases (41%) were classified as adult T-cell leukemia/lymphoma (ATLL), 103 cases (41%) as PTCL, unspecified (PTCLU), 27 cases (11%) as analplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (ALCL), 11 cases (4%) as extranodal NK/T-cell lymphoma (NKTCL), nasal type, 4 cases (2%) as angioimmunoblastic lymphoma (AIL), and 2 cases (1%) were diagnosed with ALK+ ALCL. The median age at diagnosis was 57 years (range 14–92 years); 47% of patients were >60 years. The male-to-female ratio was 1:1. ECOG performance status >1 was seen in 51%, LDH was elevated in 67%, advanced stage was seen in 73%, and >1 extranodal sites were seen in 22% of the patients. Bone marrow involvement was reported in 30% and B symptoms in 64% of patients. An International Prognostic Index (IPI) score 3–5 was seen in 55%, and a Prognostic Index for PTCLU (PIT) score of 2–4 in 63%. The median overall survival (OS) for the whole group was 10 months. The IPI score, the PIT score, ALC <1000/uL and AMC >800/uL (Figure) showed statistical significance in the univariate survival analysis (p<0.001, p<0.001, p=0.001 and p=0.001, respectively). In the multivariate analysis, PIT score and AMC >800/uL showed statistical significance (p=0.006, p=0.046, respectively). Conclusions: Monocytosis, defined as AMC >800/uL, and the PIT score were independent prognostic factors for OS in patients with aggressive, non-primary cutaneous PTCL. Disclosures: No relevant conflicts of interest to declare.

Atypical pituitary adenomas: incidence, clinical characteristics, and implications

2011 ◽  
Vol 114 (2) ◽  
pp. 336-344 ◽  
Author(s):  
Gabriel Zada ◽  
Whitney W. Woodmansee ◽  
Shakti Ramkissoon ◽  
Jordan Amadio ◽  
Vania Nose ◽  
...  
Keyword(s):  
Pituitary Adenomas ◽  
Immunohistochemical Analysis ◽  
Null Cell ◽  
Cell Adenoma ◽  
Null Cell Adenoma ◽  
Tumor Subtypes ◽  
P53 Immunoreactivity ◽  
Mib 1

Object The 2004 WHO classification of pituitary adenomas now includes an “atypical” variant, defined as follows: MIB-1 proliferative index greater than 3%, excessive p53 immunoreactivity, and increased mitotic activity. The authors review the incidence of this atypical histopathological subtype and its correlation with tumor subtype, invasion, and surgical features. Methods The records of 121 consecutive patients who underwent transsphenoidal surgery for pituitary adenomas during an 18-month period were retrospectively reviewed for evidence of atypical adenomas. Results Eighteen adenomas (15%) met the criteria for atypical lesions; 17 (94%) of the 18 were macroadenomas. On imaging, 15 (83%) demonstrated imaging evidence of surrounding invasion, compared with 45% of typical adenomas (p = 0.004). Atypical tumors occurred in 12 female (67%) and 6 male (33%) patients. Patient age ranged from 16 to 70 years (mean 48 years). Nine patients (50%) had hormonally active tumors, and 9 had nonfunctional lesions. Four (22%) of the 18 patients presented to us with recurrent tumors. Immunohistochemical analysis demonstrated the following tumor subtypes: GH-secreting adenoma with plurihormonal staining (5 patients [28%]); null-cell adenoma (5 patients [28%]); silent ACTH tumor (3 patients [17%]), ACTH-staining tumor with Cushing's disease (2 patients [11%]), prolactinoma (2 patients [11%]), and silent FSH-staining tumor (1 patient [6%]). The MIB-1 labeling index ranged from 3% to 20% (mean 7%). Conclusions Atypical tumors were identified in 15% of resected pituitary adenomas, and they tended to be aggressive, invasive macroadenomas. More longitudinal follow-up is required to determine whether surgical outcomes, potential for recurrence, or metastasis of atypical adenomas vary significantly from their typical counterparts.

scholarly journals How to Classify Pituitary Neuroendocrine Tumors (PitNET)s in 2020

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 514 ◽  
Author(s):  
Jacqueline Trouillas ◽  
Marie-Lise Jaffrain-Rea ◽  
Alexandre Vasiljevic ◽  
Gérald Raverot ◽  
Federico Roncaroli ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Early Recognition ◽  
Pituitary Tumors ◽  
Operative Management ◽  
Prognostic Impact ◽  
Null Cell ◽  
Ki 67 ◽  
Standardized Report ◽  
Proliferative Markers ◽  
Morphologic Type

Adenohypophyseal tumors, which were recently renamed pituitary neuroendocrine tumors (PitNET), are mostly benign, but may present various behaviors: invasive, “aggressive” and malignant with metastases. They are classified into seven morphofunctional types and three lineages: lactotroph, somatotroph and thyrotroph (PIT1 lineage), corticotroph (TPIT lineage) or gonadotroph (SF1 lineage), null cell or immunonegative tumor and plurihormonal tumors. The WHO 2017 classification suggested that subtypes, such as male lactotroph, silent corticotroph and Crooke cell, sparsely granulated somatotroph, and silent plurihormonal PIT1 positive tumors, should be considered as “high risk” tumors. However, the prognostic impact of these subtypes and of each morphologic type remains controversial. In contrast, the French five-tiered classification, taking into account the invasion, the immuno-histochemical (IHC) type, and the proliferative markers (Ki-67 index, mitotic count, p53 positivity), has a prognostic value validated by statistical analysis in 4 independent cohorts. A standardized report for the diagnosis of pituitary tumors, integrating all these parameters, has been proposed by the European Pituitary Pathology Group (EPPG). In 2020, the pituitary pathologist must be considered as a member of the multidisciplinary pituitary team. The pathological diagnosis may help the clinician to adapt the post-operative management, including appropriate follow-up and early recognition and treatment of potentially aggressive forms.

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.

Sign in / Sign up

Export Citation Format

Share Document