Growth-hormone (GH)- and prolactin (PRL)-secreting PitNETs (pituitary neuroendocrine tumors) are divided into multiple histological subtypes, which determine their clinical and biological variable behavior. Proliferation markers alone have a questionable degree of prediction, so we try to identify validated prognostic models as accurately as possible. (1) Background: The data available so far show that the use of staging and clinical–pathological classification of PitNETs, along with imaging, are useful in predicting the evolution of these tumors. So far, there is no consensus for certain markers that could predict tumor evolution. The application of the WHO (World Health Organisation) classification in practice needs to be further evaluated and validated. (2) Methods: We performed the CRD42023401959 protocol in Prospero with a systematic literature search in PubMed and Web of Science databases and included original full-text articles (randomized control trials and clinical trials) from the last 10 years, published in English, and the search used the following keywords: (i) pituitary adenoma AND (prognosis OR outcome OR prediction), (ii) growth hormone pituitary adenoma AND (prognosis OR outcome OR prediction), (iii) prolactin pituitary adenoma AND (prognosis OR outcome OR prediction); (iv) mammosomatotroph adenoma AND (prognosis OR outcome OR prediction). (3) Results: Two researchers extracted the articles of interest and if any disagreements occurred in the selection process, these were settled by a third reviewer. The articles were then assessed using the ROBIS bias assessment and 75 articles were included. (4) Conclusions: the clinical–pathological classification along with factors such as GH, IGF-1, prolactin levels both preoperatively and postoperatively offer valuable information.

Pituitary neuroendocrine tumors (PitNETs) are divided into multiple histological subtypes, which determine their clinical and biological variable behavior. Despite their benign evolution, in some cases, prolactin (PRL) and growth hormone (GH)-secreting PitNETs may have aggressive behavior. In this study, we investigated the potential predictive role of ER∝, alongside the clinicopathological classification of PitNETs (tumor diameter, tumor type, and tumor grade). A retrospective study was conducted with 32 consecutive cases of PRL- and mixed GH- and PRL-secreting PitNETs (5 patients with prolactinomas and 27 with acromegaly, among them, 7 patients with GH- and PRL- co-secretion) who underwent transsphenoidal intervention. Tumor specimens were histologically and immunohistochemical examined: anterior pituitary hormones, ki-67 labeling index, CAM 5.2, and ER∝; ER∝ expression was correlated with basal PRL levels at diagnosis (rho = 0.60, p < 0.01) and postoperative PRL levels (rho = 0.58, p < 0.001). In our study, the ER∝ intensity score was lower in female patients. Postoperative maximal tumor diameter correlated with Knosp grade (p = 0.02); CAM 5.2 pattern (densely/sparsely granulated/mixed densely and sparsely granulated) was correlated with postoperative PRL level (p = 0.002), and with ki-67 (p < 0.001). The IGF1 level at diagnosis was correlated with the postoperative GH nadir value in the oral glucose tolerance test (OGTT) (rho = 0.52, p < 0.05). Also, basal PRL level at diagnosis was correlated with postoperative tumor diameter (p = 0.63, p < 0.001). At univariate logistic regression, GH nadir in OGTT test at diagnostic, IGF1, gender, and invasion were independent predictors of remission for mixed GH- and PRL-secreting Pit-NETs; ER∝ can be used as a prognostic marker and loss of ER∝ expression should be considered a sign of lower differentiation and a likely indicator of poor prognosis. A sex-related difference can be considered in the evolution and prognosis of these tumors, but further studies are needed to confirm this hypothesis.

Objective. This study examined the potential use of computed tomography panoramic mandibular indices on cone beam CT (CBCT) for assessing bone density in postmenopausal women with low bone mass. Study design. The study enrolled 104 postmenopausal women who underwent dual-energy X-ray absorptiometry (DXA) using a DXA scanner and mental foramen region CBCT alongside the NewTom VGi EVO Cone Beam 3D system. We assessed the relationship between the following DXA parameters: lumbar, femoral neck, and total hip T score, bone mineral density (BMD), and lumbar trabecular bone score (TBS). The following panoramic mandibular indices were also considered: the computed tomography mandibular index superior (CTI(S)), computed tomography mandibular index inferior (CTI(I)), and computed tomography mental index (CTMI). Results. The study revealed moderate correlations between CBCT indices and BMD/TBS scores: CTMI showed the highest correlation with the femoral neck T-score (r = 0.551, p < 0.0001). TBS scores were also moderately correlated with CBCT indices: CTMI showed a moderate positive correlation with TBS (r = 0.431, p < 0.0001); CTI(S) had a similar moderate positive correlation with TBS (r = 0.421, p < 0.0001). AUC values ranged from 0.697 to 0.733 for osteoporosis versus the osteopenia/normal group and from 0.734 to 0.744 for low versus normal bone quality groups, p < 0.0001. The comparison of the values of the studied indices between low versus normal bone quality (quantified with TBS) groups showed high sensitivity but low specificity. Conclusions. CBCT-measured indices CTI(S), CTI(I), and CTMI are useful in assessing patients with low bone mass to improve, by specific treatment, the prognosis of dental implants.

Plurihormonal pituitary neuroendocrine tumors (PitNETs) are rare forms of tumors that express more than one hormone. The most common association is between growth hormone (GH) and prolactin (PRL), but other unusual combinations have been reported, such as GH and ACTH. Usually, the clinical dominance in these cases is related to GH hypersecretion. In these cases, immunohistochemistry (IHC) of transcription factors (TFs) is very useful for an accurate diagnosis. We included 42 patients diagnosed with pituitary neuroendocrine tumors (PitNETs): 37 patients with a confirmed diagnosis of acromegaly, and 5 patients with prolactinomas. All patients underwent transsphenoidal surgical intervention. We correlated the immunohistochemical features of plurihormonal PitNETs with clinical, hormonal, and imaging data. Tumor specimens were histologically and immunohistochemically examined. Based on the 2022 WHO classification, using IHC, 13 patients exhibited positive staining for more than one hormone, while unusual combinations like GH + ACTH and PRL + ACTH were also identified in other cases. Unusual cell combinations that produce hormones unrelated histogenetically, biochemically, or through regulatory mechanisms can appear and may display aggressive behavior, persistent disease, and high recurrence. We have not identified a clear correlation with the prognosis of these rare PitNETs.

Pituitary neuroendocrine tumors (PitNETs) represent a complex pathology based on numerous incompletely elucidated molecular mechanisms. Beyond tumor cells, analyzing the tumor microenvironment may help identify novel prognostic markers and therapies. A key component of this environment is the folliculo-stellate (FS) cell. We examined FS cells in 77 PitNETs obtained by transsphenoidal surgery, using glial fibrillary acidic protein (GFAP) as an immunohistochemical marker. Immunohistochemistry for anterior pituitary hormones and transcription factors was performed to accurately classify the tumors. Our study included 19 somatotroph, 16 mammosomatotroph, 5 plurihormonal PIT-1 positive, 7 corticotroph, 14 gonadotroph, 11 unusual plurihormonal, and 5 null cell PitNETs. FS cells were observed in 55 of the cases, distributed isolated, in small groups or diffuse networks. A considerable number of tumors immunopositive for more than one hormone (including associations between GH/PRL, but also unusual combinations like GH/ACTH) also contained FS cells (p < 0.01), suggesting their involvement in tumor lineages differentiation. In 27 tumors, GFAP-positive cells clustered in highly vascularized areas. Additionally, in 11 of these cases a direct interaction between endothelial cells and FS cells was noted, sustaining their potential role in tumor angiogenesis. Given their complexity, FS cells may be crucial for understanding tumorigenesis mechanisms.

Objective. The present study examined the potential use of computed tomography panoramic mandibular indices on cone beam CT (CBCT) for the assessment of bone density in postmenopausal women with low bone mass. Study design. We enrolled 104 postmenopausal women who performed dual energy X-ray absorptiometry (DXA) using a DXA scanner and mental foramen region CBCT using NewTom VGi EVO Cone Beam 3D system. We assessed the relationship between DXA parameters: lumbar, femoral neck and total hip T score, bone mineral density (BMD), and lumbar trabecular bone score (TBS) and the panoramic mandibular indices: computed tomography mandibular index superior (CTI(S)), computed tomography mandibular index inferior (CTI(I)) and computed tomography mental index (CTMI). Results. We found important correlations between the CTI(I), CTI(S) and CTMI and bone mass, quantitative evaluated as BMD and T-score and also quality using TBS score. Conclusion. CBCT measured indices CTI(S), CTI(I), CTMI are useful in assessing patients with low bone mass.