The 2017 World Health Organization (WHO) classification recognizes some subtypes of pituitary tumors as „high-risk PAs” due to their clinical aggressive behavior: the sparsely granulated somatotroph adenoma, the lactotroph adenoma in men, the Crooke's cell adenoma, the silent corticotroph adenoma, and the newly introduced plurihormonal Pit-1-positive adenoma (previously known as silent subtype III pituitary adenoma).
According to the above-mentioned classification of PAs, GH secreting PAs are divided into multiple histological subtypes, which determine their clinical and biological variable behavior: densely granulated (the most common subtype), sparsely granulated, mamosomatotroph, mixed somatotroph-lactotroph adenomas, plurihormonal adenomas, and silent somatotroph adenomas. The term somatotroph plurihormonal PIT-1 positive tumor refers to lesions with variable expression of PIT-1, GH, TSH, and/or PRL. Lactotroph PAs are divided into densely granulated, sparsely granulated, and acidophilic stem cell adenomas. There are also plurihormonal adenomas with unusual immunohistochemical combinations, such as ACTH.GH and PRL/GH. Unlike other NETs, PitNETs are not stratified into grades based on their Ki67 proliferation index; there are other better biomarkers of aggressive behavior.
The recent (and debated) proposal of the European Pituitary Pathology Group (EPPG) to replace the term „adenoma” with that of neuroendocrine pituitary tumor reminds the importance of cell lineages and transcription factors in the development of these tumors. The proposal is based on the fact that these tumors may have an unpredictable evolution, similar to that of classical neuroendocrine tumors, but this notion is currently being debated, as other research groups do not fully agree with it. The same European research group states the important role of pathology in the prediction of PAs outcome using histology associated with immunohistochemistry (IHC) and the expression of transcription factors, including these in their five-tiered prognostic classification, along with Ki-67 labeling index, p53, and O6-methylguanine-DNA methyltransferase (MGMT) expression, among others. Also, there are several different opinions among researchers about the methods used to evaluate these markers: immunohistochemistry versus real-time PCR.
Predicting the evolution of these tumors can be a real challenge. Proliferation markers alone have a questionable degree of prediction, so we try to create a model as accurately as possible. The data available so far shows that the use of staging and clinical-pathological classification of pituitary adenomas, along with imaging, are useful in predicting the evolution of these tumors.
Clinico-pathological classification based on tumor diameter, immunohistochemistry, invasion, and presence of proliferation markers (ki-67, number of mitoses, p53) can predict the evolution of pituitary adenomas. The granulation of GH-secreting pituitary adenomas, p21 expression, and SSTR2 receptors are determinants of their prognosis (favorable/intermediate/unfavorable). Also, the response to treatment is dependent on the histological subtype. It is well known that the presence of SSTR2-type somatostatin receptors correlates positively with response to octreotide treatment in patients with GH-secreting pituitary adenomas. Invasion is the major prognostic factor for the evolution of pituitary adenomas. In the case of prolactinomas, there is a proven correlation between ERα expression, tumor diameter, prolactin level, and the treatment outcome.
The identification of prognostic factors will allow the application of personalized therapies in patients diagnosed with pituitary adenomas, thus increasing the success rate of treatment and improving survival and quality of life.
With this article collection, Topic Editors aim to collect manuscripts focusing on:
- The identification of predictors of evolution and response to treatment for pituitary adenomas secreting GH, PRL and those with mixed GH / PRL secretion;
- The study and identification of markers for resistance to treatment;
- The recurrence and validation of the prognostic value of structural and morphological classification;
- The validation of the prognostic value of immunohistochemical markers (hormone immunostaining, Ki-67 labelling index, p53, MGMT, ERα);
- Prognostic models, based on artificial intelligence, highlighting how this can be a useful tool in the diagnosis and personalized therapy of pituitary adenomas.
All pituitary tumors must be classified based on cell lineage, cell type, hormone production, and LMWK low molecular weight cytokeratin expression, ERα, GATA3 expression. Interestingly, there can exist a hormonal variability in these tumors. A standardized report based on all these characteristics can be created and used, internationally. The different results obtained by researchers (clinical studies, meta-analyses etc) can be a valuable tool to establish a prognostic model and identifying new treatment targets.
The 2017 World Health Organization (WHO) classification recognizes some subtypes of pituitary tumors as „high-risk PAs” due to their clinical aggressive behavior: the sparsely granulated somatotroph adenoma, the lactotroph adenoma in men, the Crooke's cell adenoma, the silent corticotroph adenoma, and the newly introduced plurihormonal Pit-1-positive adenoma (previously known as silent subtype III pituitary adenoma).
According to the above-mentioned classification of PAs, GH secreting PAs are divided into multiple histological subtypes, which determine their clinical and biological variable behavior: densely granulated (the most common subtype), sparsely granulated, mamosomatotroph, mixed somatotroph-lactotroph adenomas, plurihormonal adenomas, and silent somatotroph adenomas. The term somatotroph plurihormonal PIT-1 positive tumor refers to lesions with variable expression of PIT-1, GH, TSH, and/or PRL. Lactotroph PAs are divided into densely granulated, sparsely granulated, and acidophilic stem cell adenomas. There are also plurihormonal adenomas with unusual immunohistochemical combinations, such as ACTH.GH and PRL/GH. Unlike other NETs, PitNETs are not stratified into grades based on their Ki67 proliferation index; there are other better biomarkers of aggressive behavior.
The recent (and debated) proposal of the European Pituitary Pathology Group (EPPG) to replace the term „adenoma” with that of neuroendocrine pituitary tumor reminds the importance of cell lineages and transcription factors in the development of these tumors. The proposal is based on the fact that these tumors may have an unpredictable evolution, similar to that of classical neuroendocrine tumors, but this notion is currently being debated, as other research groups do not fully agree with it. The same European research group states the important role of pathology in the prediction of PAs outcome using histology associated with immunohistochemistry (IHC) and the expression of transcription factors, including these in their five-tiered prognostic classification, along with Ki-67 labeling index, p53, and O6-methylguanine-DNA methyltransferase (MGMT) expression, among others. Also, there are several different opinions among researchers about the methods used to evaluate these markers: immunohistochemistry versus real-time PCR.
Predicting the evolution of these tumors can be a real challenge. Proliferation markers alone have a questionable degree of prediction, so we try to create a model as accurately as possible. The data available so far shows that the use of staging and clinical-pathological classification of pituitary adenomas, along with imaging, are useful in predicting the evolution of these tumors.
Clinico-pathological classification based on tumor diameter, immunohistochemistry, invasion, and presence of proliferation markers (ki-67, number of mitoses, p53) can predict the evolution of pituitary adenomas. The granulation of GH-secreting pituitary adenomas, p21 expression, and SSTR2 receptors are determinants of their prognosis (favorable/intermediate/unfavorable). Also, the response to treatment is dependent on the histological subtype. It is well known that the presence of SSTR2-type somatostatin receptors correlates positively with response to octreotide treatment in patients with GH-secreting pituitary adenomas. Invasion is the major prognostic factor for the evolution of pituitary adenomas. In the case of prolactinomas, there is a proven correlation between ERα expression, tumor diameter, prolactin level, and the treatment outcome.
The identification of prognostic factors will allow the application of personalized therapies in patients diagnosed with pituitary adenomas, thus increasing the success rate of treatment and improving survival and quality of life.
With this article collection, Topic Editors aim to collect manuscripts focusing on:
- The identification of predictors of evolution and response to treatment for pituitary adenomas secreting GH, PRL and those with mixed GH / PRL secretion;
- The study and identification of markers for resistance to treatment;
- The recurrence and validation of the prognostic value of structural and morphological classification;
- The validation of the prognostic value of immunohistochemical markers (hormone immunostaining, Ki-67 labelling index, p53, MGMT, ERα);
- Prognostic models, based on artificial intelligence, highlighting how this can be a useful tool in the diagnosis and personalized therapy of pituitary adenomas.
All pituitary tumors must be classified based on cell lineage, cell type, hormone production, and LMWK low molecular weight cytokeratin expression, ERα, GATA3 expression. Interestingly, there can exist a hormonal variability in these tumors. A standardized report based on all these characteristics can be created and used, internationally. The different results obtained by researchers (clinical studies, meta-analyses etc) can be a valuable tool to establish a prognostic model and identifying new treatment targets.