A standardised diagnostic approach to pituitary neuroendocrine tumours (PitNETs): a European Pituitary Pathology Group (EPPG) proposal

Villa, Chiara; Vasiljevic, Alexandre; Jaffrain-Rea, Marie Lise; Ansorge, Olaf; Asioli, Sofia; Barresi, Valeria; Chinezu, Laura; Gardiman, Marina Paola; Lania, Andrea; Лапшина, А М; Poliani, Pietro Luigi; Reiniger, Lilla; Righi, Alberto; Saeger, Wolfgang; Soukup, Jiří; Theodoropoulou, Marily; Uccella, Silvia; Trouillas, Jacqueline; Roncaroli, Federico

doi:10.1007/s00428-019-02655-0

Cited by 77 publications

(76 citation statements)

References 17 publications

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“…While the hyperprolactinemia found in two of the PRL-negative adenomas was likely caused by compression of the hypothalamus by the tumour mass, which inhibits dopamine secretion and thereby promotes PRL secretion [24], both tumour volume and the percentage of macroadenomas were not significantly different between patients with hyper-and normoprolactinemia in our study. Our findings suggest that hyperprolactinemia in acromegaly patients is likely to be caused by co-secretion of PRL by the tumour and less likely by pituitary stalk compression and validate the cutoff of ≥ 10 % PRL-positive cells as a criterion for the histological diagnosis of a somatolactotroph tumour, as proposed by Villa et al [22]. While Trouillas et al found a correlation between serum PRL levels and the percentage of cells with a positive PRL IHC [24], four other studies contradict this finding [13,14,25,26].…”

Section: Discussionsupporting

confidence: 86%

“…Immunohistochemistry (IHC) was performed according to standard methods using antibodies against GH and PRL (GH Ventana Roche -Catalogue number 760-2804 -polyclonal and PRL Ventana Roche -Catalogue number 760-2803 -polyclonal) and positive cells were counted optically. Tumours were classified as somatotroph adenomas if they stained positive for GH and, according to Villa et al [22], classified as somatolactotroph tumours if there is both positive staining for GH and at least 10 % of the cells for PRL (see ▶ Figs. 1 and 2 for an example of an adenoma with respectively < 10 % and ≥ 10 % PRL-positive cells).…”

Section: Tumour Characteristicsmentioning

confidence: 99%

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Hyperprolactinemia in Acromegaly is Related to Prolactin Secretion by Somatolactotroph Tumours

et al. 2020

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The aim of this study is to assess differences in patient characteristics, tumour characteristics and hormone levels between acromegalic patients with and without hyperprolactinemia. 44 patients of the University Hospital of Brussels, Belgium with acromegaly who were diagnosed between January 2007 and July 2018 were included in this study. Nineteen patients were classified in the hyperprolactinemia group and 25 patients were classified in the normoprolactinemia group. No significant differences between acromegalic patients with and without hyperprolactinemia were found in age at diagnosis, gender, presence of hyperprolactinemia symptoms, insulin-like growth factor 1, growth hormone and testosterone levels, tumour volume, tumour invasiveness, immunohistochemistry of growth hormone and prolactin, Ki-67 index and mitotic index. However, for a cut-off of 10% of prolactin-positive cells, there was a trend towards a higher percentage of prolactin-positive tumours in hyperprolactinemia patients (p=0.054) and higher mean prolactin level in case of positive prolactin immunostaining (p=0.007)). In our study there were no differences in characteristics between acromegaly patients with hyper- and normoprolactinemia. An association between the serum prolactin level and the positivity of prolactin immunohistochemistry of the adenoma tissue was found. The absence of a difference in tumour volume between patients with hyper- and normoprolactinemia suggests that the hyperprolactinemia is likely to be caused by the co-secretion of growth hormone and prolactin by the tumour. Finally, for the first time, the cut-off of 10% of prolactin cells was validated for the diagnosis of somatolactotroph tumours in acromegaly.

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Section: Discussionsupporting

confidence: 86%

Section: Tumour Characteristicsmentioning

confidence: 99%

Hyperprolactinemia in Acromegaly is Related to Prolactin Secretion by Somatolactotroph Tumours

et al. 2020

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“…However, it will be of tremendous importance to not only stop considering gonadotroph tumors as simply NF-PitNETs (instead of a distinct group of tumors) and hormone-negative tumors as a homogenous group [2,3], but also to start acknowledging that gonadotroph tumors themselves are heterogeneous. Indeed, our study comes to add to the growing literature on the heterogeneity of PitNETs and on the need to continue to refine the histological classification of these tumors [3,21].…”

Section: Discussionmentioning

confidence: 99%

“…Pituitary adenomas, recently renamed pituitary neuroendocrine tumors (PitNETs) [1,2], are common neoplasms, representing 10-20% of all intracranial tumors. Of these, gonadotroph tumors represent approximatively one-third [3,4].…”

Section: Introductionmentioning

confidence: 99%

Gonadotroph Tumors Show Subtype Differences that Might Have Implications for Therapy

Ilie

Vasiljevic

Louvet

et al. 2020

Cancers

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Gonadotroph tumors, although frequent, are poorly studied and understood, being usually included in the larger nonfunctioning pituitary neuroendocrine tumors (PitNETs) group. Moreover, in comparison to the other types of PitNETs, no established medical treatment is currently available for gonadotroph tumors. Here, we performed a retrospective study and analyzed the clinicopathological characteristics of 98 gonadotroph tumors operated in a single large pituitary center. Although being larger in men (p = 0.01), the aggressiveness of gonadotroph tumors did not appear to be sex-related. LH tumors were rare (4/98) and exclusively encountered in men. Somatostatin receptor type 5 (SST5) was absent in all analyzed tumors. The immunoreactive score (IRS) of somatostatin receptor type 2 (SST2) and of estrogen receptor alpha (ERα) was associated with the histological subtype (p = 0.01 and p = 0.02). IRS ERα correlated moderately with IRS SST2 in all (rho = 0.44, adjusted p-value = 0.0001) and in male (rho = 0.51, adjusted p-value = 0.0002) patients, and with follicle-stimulating hormone (FSH) percentage in all (rho = 0.40, adjusted p-value = 0.0005) and in female (rho = 0.58, adjusted p-value = 0.004) patients. In conclusion, gonadotroph tumors exhibit histological characteristics pinpointing the existence of several subtypes. Their heterogeneity warrants further investigations and may have to be taken into account when studying these tumors and investigating treatment options.

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“…To overcome these limits, a grading system based on the combination of clinical and histopathological features, which correlates with high accuracy with the clinical outcome in term of recurrence rate and disease persistence, has been recently proposed by Trouillas et al [137]. This system has been validated in independent reports [61,138] and included as integrated diagnostic information within the algorithm proposed for a standardized diagnostic approach to PitNETs by the European Pituitary Pathology Group (EPPG) [139]. The proposed grading system is basically founded on three major tumor features related to tumor size, proliferation, and invasiveness, while expression of p53, previously adopted as a potential marker of PitNET aggressiveness, has been confined to a minor role, since the low frequency of p53 detection by immunohistochemistry indicates that it is inadequate as a routine marker of invasiveness.…”

Section: Pathological and Molecular Considerationsmentioning

confidence: 99%

Pituitary Adenomas and Invasiveness from Anatomo-Surgical, Radiological, and Histological Perspectives: A Systematic Literature Review

Serioli

Doglietto

Fiorindi

et al. 2019

Cancers

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Invasiveness in pituitary adenomas has been defined and investigated from multiple perspectives, with varying results when its predictive value is considered. A systematic literature review, following PRISMA guidelines, was performed, searching PubMed and Scopus databases with terms that included molecular markers, histological, radiological, anatomical and surgical data on invasiveness of pituitary adenomas. The results showed that differing views are still present for anatomical aspects of the sellar region that are relevant to the concept of invasiveness; radiological and histological diagnoses are still limited, but might improve in the future, especially if they are related to surgical findings, which have become more accurate thanks to the introduction of the endoscope. The aim is to achieve a correct distinction between truly invasive pituitary adenomas from those that, in contrast, present with extension in the parasellar area through natural pathways. At present, diagnosis of invasiveness should be based on a comprehensive analysis of radiological, intra-operative and histological findings.

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A standardised diagnostic approach to pituitary neuroendocrine tumours (PitNETs): a European Pituitary Pathology Group (EPPG) proposal

Cited by 77 publications

References 17 publications

Hyperprolactinemia in Acromegaly is Related to Prolactin Secretion by Somatolactotroph Tumours

Hyperprolactinemia in Acromegaly is Related to Prolactin Secretion by Somatolactotroph Tumours

Gonadotroph Tumors Show Subtype Differences that Might Have Implications for Therapy

Pituitary Adenomas and Invasiveness from Anatomo-Surgical, Radiological, and Histological Perspectives: A Systematic Literature Review

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