Silent somatotroph tumour revisited from a study of 80 patients with and without acromegaly and a review of the literature

Chinezu, Laura; Vasiljevic, Alexandre; Trouillas, Jacqueline; Lapoirie, Marion; Jouanneau, Emmanuel; Raverot, Gérald

doi:10.1530/eje-16-0738

Cited by 36 publications

(22 citation statements)

References 23 publications

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“…Clinically, NF tumors belong mainly to the gonadotroph type and are immunoreactive for FSH and LH subunits [10]. They differ from the much rarer silent corticotroph [11], silent somatotroph [12], silent TSH [13] and "poorly differentiated monomorphous plurihormonal PIT1 lineage" tumors [14]. In the latter, the diagnosis is based on the expression of ACTH, GH, TSH or GH/PRL seen by immunohistochemistry (IHC).…”

Section: Clinical Classificationsmentioning

confidence: 99%

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

Trouillas

Jaffrain-Rea

Vasiljevic

et al. 2020

Cancers

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139

104

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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.

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Section: Clinical Classificationsmentioning

confidence: 99%

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

Trouillas

Jaffrain-Rea

Vasiljevic

et al. 2020

Cancers

Self Cite

139

104

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Section: Pituitary Lineage Specific Classification Of Nf-pitnetsmentioning

confidence: 99%

“…Non-functioning/silent somatotroph tumors are Pit-1 and GH immunoreactive tumors without clinical signs of acromegaly [ 2 , 52 , 53 ]. They represent 2–3% of all pituitary tumors [ 53 ]. Similar to their much more frequent functioning counterparts, they can be divided into sparsely and densely granulated somatotroph tumors based on low molecular weight cytokeratin (LMWCK) [CK7/8 (Cam5.2) and CK18] staining, demonstrating either fibrous bodies or diffuse cytoplasmic pattern (Table 1 ) [ 2 , 53 ].…”

Section: Pituitary Lineage Specific Classification Of Nf-pitnetsmentioning

confidence: 99%

“…They represent 2–3% of all pituitary tumors [ 53 ]. Similar to their much more frequent functioning counterparts, they can be divided into sparsely and densely granulated somatotroph tumors based on low molecular weight cytokeratin (LMWCK) [CK7/8 (Cam5.2) and CK18] staining, demonstrating either fibrous bodies or diffuse cytoplasmic pattern (Table 1 ) [ 2 , 53 ]. NF-somatotroph PitNETs are predominantly sparsely granulated, in contrast to functioning somatotroph PitNETs, where the frequency of sparsely and densely granulated tumors is equal [ 52 , 53 ] or in favor of densely granulated subtype [ 54 , 55 ].…”

Section: Pituitary Lineage Specific Classification Of Nf-pitnetsmentioning

confidence: 99%

“…They have a lower proportion of GH-immunoreactive cells, which suggests lower differentiation. Majority of silent somatotroph tumors co-express prolactin [ 53 ]. Sparsely granulated somatotroph tumors are, according to the WHO classification [ 2 ], designated as more aggressive tumors based on several studies demonstrating that they are usually larger and more invasive compared to the densely granulated subtype [ 54 – 56 ].…”

Section: Pituitary Lineage Specific Classification Of Nf-pitnetsmentioning

confidence: 99%

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Histopathological classification of non-functioning pituitary neuroendocrine tumors

2017

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Non-functioning pituitary neuroendocrine tumors do not cause endocrine symptoms related to hypersecretion of adenohypophyseal hormones and are clinically characterized by symptoms due to growing sellar tumor mass. Histopathological classification of this tumor group has always been challenging due to their heterogeneity, limited knowledge on their biology, and diverse methodological problems. We have searched PubMed database for data related to the histopathological classification of non-functioning pituitary tumors and methods for its application. Principles of the classification and grading presented in the recently released 4th edition of the World Health Organization classification of endocrine tumors have been summarized. Based on the expression of anterior pituitary hormones and pituitary specific transcription factors, gonadotroph tumors dominate within the group of clinically non-functioning tumors, followed by corticotroph type; however, other less common types of the non-functioning tumors can be identified. Assessment of tumor cell proliferation is important to identify “high-risk adenomas.” A few subtypes of non-functioning tumors belong to the category of potentially aggressive tumors, independent of the cell proliferation rate. Here, we present up to date criteria for the classification of clinically non-functioning pituitary tumors, offer a diagnostic approach for the routine clinical use, and emphasize a need for inclusion of prognostic and predictive markers in the classification.

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TGF‐β1/Smad2/3 signaling pathway modulates octreotide antisecretory and antiproliferative effects in pituitary somatotroph tumor cells

Picech

Sosa

Pérez

et al. 2021

Journal Cellular Physiology

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Octreotide (OCT) is used to inhibit hormone secretion and growth in somatotroph tumors, although a significant percentage of patients are resistant. It has also been tested in nonfunctioning (NF) tumors but with poor results, with these outcomes having been associated with SSTR2 levels and impaired signaling. We investigated whether OCT inhibitory effects can be improved by TGF‐β1 in functioning and nonfunctioning somatotroph tumor cells. OCT effects on hormone secretion and proliferation were analyzed in the presence of TGF‐β1 in WT and SSTR2‐overexpressing secreting GH3 and silent somatotroph tumor cells. The mechanism underlying these effects was assessed by studying SSTR and TGFβR signaling pathways mediators. In addition, we analyzed the effects of OCT/TGF‐β1 treatment on tumor growth and cell proliferation in vivo. The inhibitory effects of OCT on GH‐ and PRL‐secretion and proliferation were improved in the presence of TGF‐β1, as well as by SSTR2 overexpression. The OCT/TGF‐β1 treatment induced downregulation of pERK1/2 and pAkt, upregulation of pSmad3, and inhibition of cyclin D1. In vivo experiments showed that OCT in the presence of TGF‐β1 blocked tumor volume growth, decreased cell proliferation, and increased tumor necrosis. These results indicate that SSTR2 levels and the stimulation of TGF‐β1/TGFβR/Smad2/3 pathway are important for strengthening the antiproliferative and antisecretory effects of OCT.

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Silent somatotroph tumour revisited from a study of 80 patients with and without acromegaly and a review of the literature

Cited by 36 publications

References 23 publications

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

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

Histopathological classification of non-functioning pituitary neuroendocrine tumors

TGF‐β1/Smad2/3 signaling pathway modulates octreotide antisecretory and antiproliferative effects in pituitary somatotroph tumor cells

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