Myeloid Sarcoma of the Breast as Blast Phase of JAK2-Mutated (Val617Phe Exon 14p) Essential Thrombocythemia: A Case Report and a Systematic Literature Review.

INTRODUCTION: Myeloid sarcoma (MS) is a mass-forming proliferation of myeloid blasts. Frequently, it arises as blast phase of pre-existing myeloproliferative, myelodysplastic disorders or consequent to bone marrow transplant. Its molecular characterization has become an increasingly important requirement for the diagnostic definition of this solid leukemia. CASE PRESENTATION: Our case report concerns an MS arising in the breast of a woman with a previous diagnosis of JAK2-mutated essential thrombocythemia (Val617Phe exon 14p) mimicking, on histology, a lobular carcinoma of the breast. The immunohistochemical study of the neoplasm provided the key that solved the diagnostic doubt and the immunohistochemical evaluation of NPM protein expression, which turn out to be negative, provided a clear indication on the molecular status and prognosis of the disease. A year later, the neoplasm relapsed in the pelvic area. DISCUSSION: This diagnostic challenge led us to review the literature of the past 10 years concerning MS of the breast. To the best of our knowledge, this was the first case of MS of the breast occurring in a patient with a history of essential thrombocythemia and recurred in the pelvic region.

Malignant intraventricular meningioma: literature review and case report.

Malignant intraventricular meningiomas (IVMs) are very rare with only a few reported cases. A midline search up to December 2020 selected 40 articles for a total of 65 patients. The inclusion criteria were series and case reports in English language, as well as papers written in other languages, but with abstracts written in English. Malignant IVMs at the first diagnosis (group A, 50 patients) and those with anaplastic transformation from previous WHO grades I and II tumors (group B, 15 patients) were separately analyzed. The unique personal case among 1285 meningiomas (0.078%) is also added. Malignant IVMs mainly occur in women (61%) with a median age of 45 years and are mainly located in the lateral ventricle (93%) and trigonal region (74%), with no cases in the fourth ventricle. Irregular borders (80%), heterogeneous enhancement (83%), and perilesional edema (76%) are the most frequent radiological findings. The histology was mainly pure anaplastic (85%), whereas papillary (7%), rhabdoid (5%), and mixed forms (3%) are very rare. The CSF spread was found in 60% of the cases. The prognosis is very dismal, with an overall median survival of 17.5 months after surgery for the anaplastic forms. Malignant IVMs at initial diagnosis (group A) show better overall survival (25 months) than those occurring from anaplastic transformation of lower grade tumors (group B) (10.1 months).

Periprostatic adipose tissue promotes prostate cancer resistance to docetaxel by paracrine IGF-1 upregulation of TUBB2B beta-tubulin isoform.

Growing evidence supports the pivotal role played by periprostatic adipose tissue (PPAT) in prostate cancer (PCa) microenvironment. We investigated whether PPAT can affect response to Docetaxel (DCTX) and the mechanisms associated. Conditioned medium was collected from the in vitro differentiated adipocytes isolated from PPAT which was isolated from PCa patients, during radical prostatectomy. Drug efficacy was studied by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide citotoxicity assay. Culture with CM of human PPAT (AdipoCM) promotes DCTX resistance in two different human prostate cancer cell lines (DU145 and PC3) and upregulated the expression of BCL-xL, BCL-2, and TUBB2B. AG1024, a well-known IGF-1 receptor inhibitor, counteracts the decreased response to DCTX observed in presence of AdipoCM and decreased TUBB2B expression, suggesting that a paracrine secretion of IGF-1 by PPAT affect DCTX response of PCa cell. Collectively, our study showed that factors secreted by PPAT elicits DCTX resistance through antiapoptotic proteins and TUBB2B upregulation in androgen independent PCa cell lines. These findings reveal the potential of novel therapeutic strategies targeting adipocyte-released factors and IGF-1 axis to overcome DCTX resistance in patients with PCa.

From microbiota toward gastro-enteropancreatic neuroendocrine neoplasms: Are we on the highway to hell?

Gut microbiota is represented by different microorganisms that colonize the intestinal tract, mostly the large intestine, such as bacteria, fungi, archaea and viruses. The gut microbial balance has a key role in several functions. It modulates the host's metabolism, maintains the gut barrier integrity, participates in the xenobiotics and drug metabolism, and acts as protection against gastro-intestinal pathogens through the host's immune system modulation. The impaired gut microbiota, called dysbiosis, may be the result of an imbalance in this equilibrium and is linked with different diseases, including cancer. While most of the studies have focused on the association between microbiota and gastrointestinal adenocarcinomas, very little is known about gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs). In this review, we provide an overview concerning the complex interplay between gut microbiota and GEP NENs, focusing on the potential role in tumorigenesis and progression in these tumors.

Fractional Microablative CO2 Laser-Related Histological Changes on Vulvar Tissue in Patients With Genitourinary Syndrome of Menopause.

BACKGROUND AND OBJECTIVES: Fractional CO2 laser has been proposed as an effective treatment for the genitourinary syndrome of menopause (GSM). However, the effects of laser treatment on vulvar tissue have never been assessed. We aimed to assess histological changes related to fractional CO2 laser in vulvar tissue from GSM patients. STUDY DESIGN/MATERIALS AND METHODS: A single-center observational prospective cohort study was performed enrolling all GSM patients from July 2017 to October 2018. Patients underwent three outpatient vulvovaginal applications of fractional CO2 laser and vulvar biopsy before and after treatment. Rates of histological changes in vulvar tissue, the difference in means of Vulva Health Index (VuHI), Vaginal Health Index (VHI), Visual Analogue Scale scores for GSM symptoms, and procedure-related pain, and rate of patient's overall satisfaction with treatment were assessed. Univariate comparisons between continuous variables were performed by using the paired t-test (α error = 0.05). RESULTS: Of 20 enrolled patients, 18 underwent all laser applications, and 15 underwent both vulvar biopsies. 93.3% of patients showed remodeling of vulvar connective tissue; 80% showed improvement in vulvar epithelium trophism and 86.7% showed neovascularization. Differences in means between before and after treatment were significant for VuHI, VHI, and all GSM symptoms. Means ± standard deviation of the degree of pain at each laser application were 4.4 ± 0.9, 3.7 ± 1.6, and 2.9 ± 1.9. The rate of overall satisfaction with the treatment was 72.2%. CONCLUSIONS: Fractional CO2 laser leads to a restoration of the normal architecture of vulvar tissue, with significant improvement in GSM-related signs and symptoms, and overall satisfaction with the treatment in most GSM patients. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Should endometrial biopsy under direct hysteroscopic visualization using the grasp technique become the new gold standard for the preoperative evaluation of the patient with endometrial cancer?

OBJECTIVE: To investigate the diagnostic accuracy of endometrial biopsy performed with hysteroscopic direct visualization using the "grasp technique" for the detection of endometrial carcinoma (EC) histology type and tumor grade. METHODS: A cross-sectional study including the clinical and pathology records of patients with confirmed EC who underwent definitive surgery at University of Naples was performed. The preoperative diagnosis of endometrial tumor type and grade obtained using the hysteroscopy grasp technique was correlated with the final pathology specimens. Those results were compared to the diagnostic accuracy of the biopsies collected in a cohort of patients who underwent preoperative diagnostic hysteroscopy followed by blind endometrial biopsy using the Novak curette with subsequent surgical definitive treatment at University of Pisa. Statistical analysis was based on frequency data and diagnostic agreement of the pathology results. RESULTS: A total of 129 patients were included in the final analysis. An agreement rate of 104/106 (98.1%) for endometrioid type and 15/23 (65.2%) for non-endometrioid type was obtained between preoperative hysteroscopic grasp endometrial biopsy specimens and the final pathology with a coefficient k for G1, G2 and G3 tumors of 0.928, 0.925 and 0.974, respectively. When compared to 121 patients undergoing preoperative blind Novak endometrial biopsy, the hysteroscopic grasp technique was superior in agreement rates for tumor histotype [diagnostic accuracy (0.922 vs 0.890); K value (0.705 vs 0.642)] and grade when in presence of endometrioid type EC (K Cohen 0.354 for G1, 0.263 for G2 and 0.488 for G3). CONCLUSIONS: Preoperative hysteroscopic guided "grasp" endometrial biopsy provides a more accurate diagnosis of EC histology type and tumor grade when in presence of endometrioid type tumor compared to blind endometrial biopsy obtained using the Novak curette.

Machine learning assisted DSC-MRI radiomics as a tool for glioma classification by grade and mutation status.

BACKGROUND: Combining MRI techniques with machine learning methodology is rapidly gaining attention as a promising method for staging of brain gliomas. This study assesses the diagnostic value of such a framework applied to dynamic susceptibility contrast (DSC)-MRI in classifying treatment-naïve gliomas from a multi-center patients into WHO grades II-IV and across their isocitrate dehydrogenase (IDH) mutation status. METHODS: Three hundred thirty-three patients from 6 tertiary centres, diagnosed histologically and molecularly with primary gliomas (IDH-mutant = 151 or IDH-wildtype = 182) were retrospectively identified. Raw DSC-MRI data was post-processed for normalised leakage-corrected relative cerebral blood volume (rCBV) maps. Shape, intensity distribution (histogram) and rotational invariant Haralick texture features over the tumour mask were extracted. Differences in extracted features across glioma grades and mutation status were tested using the Wilcoxon two-sample test. A random-forest algorithm was employed (2-fold cross-validation, 250 repeats) to predict grades or mutation status using the extracted features. RESULTS: Shape, distribution and texture features showed significant differences across mutation status. WHO grade II-III differentiation was mostly driven by shape features while texture and intensity feature were more relevant for the III-IV separation. Increased number of features became significant when differentiating grades further apart from one another. Gliomas were correctly stratified by mutation status in 71% and by grade in 53% of the cases (87% of the gliomas grades predicted with distance less than 1). CONCLUSIONS: Despite large heterogeneity in the multi-center dataset, machine learning assisted DSC-MRI radiomics hold potential to address the inherent variability and presents a promising approach for non-invasive glioma molecular subtyping and grading.

Recurrence of spinal meningiomas: analysis of the risk factors.

Objective: Spinal meningiomas are slow-growing tumors with low recurrence rate after complete resection. The aim of this study is to investigate the risk factors correlated to the recurrence.Material and Methods: Six patients with spinal WHO grade I meningiomas which recurred after complete resection were reviewed and compared to 50 patients with no recurrence; the data were also compared with those of 50 intracranial meningiomas which recurred and 50 which did not recur after complete resection. The investigated factors included age and sex, tumor location and size, type of arachnoid interface, entity of resection (Simpson I or II), tumor consistency and vascularity, histological type, Ki-67 MIB-1, progesterone receptor (PR) and estrogen receptor (ER) expression. The data were statistically analyzed with the Kaplan-Meier method.Results: The statistical analysis showed that the presence of arachnoidal invasion (p = 0.023) and higher Ki-67 LI (p < 0.0001) were the only two significant risk factors for recurrence for both spinal and intracranial meningiomas. Large tumor size (p = 0.012), Simpson grade II resection (p = 0.03) and the absence of PR expression (p < 0.0001) were significant risk factors for recurrence of intracranial but not spinal meningiomas. Finally, age and sex, tumor location, consistency and vascularity, histological type, and ER expression were not correlated to recurrence for both localizations.Conclusions: The proliferation index Ki-67 and the arachnoid invasion are the risk factors for recurrence of spinal meningiomas, whereas tumor size, dural resection and PR expression are not significant. The small tumor size and the limited dural invasion may contribute to explain the lower recurrence rate.

Multicentric and diffuse recurrences of meningiomas.

Background: Meningiomas recur with a rate of 10-32% at 10 years. Several features influence the risk of recurrence.Objective: To define the pathological and surgical features at risk of multicentric-diffuse versus local-peripheral recurrence.Methods: Thirty-three patients operated on for intracranial meningiomas who experienced multicentric-diffuse recurrence were retrospectively analyzed. The data of these patients were compared to those of 50 patients who experienced local-peripheral recurrence. The analyzed factors included age and sex, tumor location and shape, brain-tumor interface, entity of resection, WHO grade, Ki67 MIB1, progesterone receptor (PR) expression, number of reoperations, progression of WHO grade, and outcome.Results: Meningiomas which recurred in multicentric-diffuse pattern showed at initial surgery a significantly higher rate of flat-shaped tumors (p = .0008) and of cases with Ki67 Li ≥ 4% (p = .037) than those which recurred in localized-peripheral pattern, whereas other factors did not significantly differ. Among patients with multicentric-diffuse recurrences, 25 underwent one to three reoperations; 17 among them (66%) are alive with local tumor control or slow progression 2-25 years after the initial surgery versus only 2 out of 8 who did not undergo surgery.Conclusions: Flat-shaped meningiomas and those with Ki67 Li ≥ 4% are at higher risk of multicentric-diffuse recurrence. Multiple reoperations over a period of several years may obtain rather long survivals in selected patients with prevalent intradural, not anaplastic tumors and not too extensive dural infiltration.

A challenging diagnosis of mesenchymal neoplasm of the colon: colonic dedifferentiated liposarcoma with lymph node metastases-a case report and review of the literature.

PURPOSE: We report a case of primitive colonic dedifferentiated liposarcoma along with lymph node metastases. METHODS: The patient's clinical, radiologic, surgical, and histologic data were reviewed, as well as the literature on colonic dedifferentiated liposarcoma with a focus on the incidence of lymph node metastasis in gastrointestinal sarcomas and on the differential diagnosis with other spindle cell tumors in the gastrointestinal tract. RESULTS: A 53-year-old man was referred to our hospital with a 3 year-history of pain on the right back that was refractory to drugs. He performed an abdominal computed tomography scan which revealed a colonic wall thickening in the hepatic flexure and a few serosal nodularities. With these findings, the patient underwent an extended right hemicolectomy. On histopathologic examination, it turned out to be a colonic dedifferentiated liposarcoma with lymph node metastases. CONCLUSIONS: The present case was a challenging diagnosis both at presurgical and histopathological level because it strongly mimicked a colonic adenocarcinoma. This was due to non-specific clinical and radiological presentation, to the non-characteristic histologic morphology and to the misleading presence of lymph node metastases. Malignant stromal tumors of the gastrointestinal tract beyond gist are fairly rare entities. Colonic dedifferentiated liposarcoma must be kept in mind and must be considered in the differential diagnosis of gastrointestinal tumors.

Prediction of high proliferative index in pituitary macroadenomas using MRI-based radiomics and machine learning.

PURPOSE: Pituitary adenomas are among the most frequent intracranial tumors. They may exhibit clinically aggressive behavior, with recurrent disease and resistance to multimodal therapy. The ki-67 labeling index represents a proliferative marker which correlates with pituitary adenoma aggressiveness. Aim of our study was to assess the accuracy of machine learning analysis of texture-derived parameters from pituitary adenomas preoperative MRI for the prediction of ki-67 proliferation index class. METHODS: A total of 89 patients who underwent an endoscopic endonasal procedure for pituitary adenoma removal with available ki-67 labeling index were included. From T2w MR images, 1128 quantitative imaging features were extracted. To select the most informative features, different supervised feature selection methods were employed. Subsequently, a k-nearest neighbors (k-NN) classifier was employed to predict macroadenoma high or low proliferation index. Algorithm validation was performed with a train-test approach. RESULTS: Of the 12 subsets derived from feature selection, the best performing one was constituted by the 4 highest correlating parameters at Pearson's test. These all showed very good (ICC ≥ 0.85) inter-observer reproducibility. The overall accuracy of the k-NN in the test group was of 91.67% (33/36) of correctly classified patients. CONCLUSIONS: Machine learning analysis of texture-derived parameters from preoperative T2 MRI has proven to be effective for the prediction of pituitary macroadenomas ki-67 proliferation index class. This might aid the surgical strategy making a more accurate preoperative lesion classification and allow for a more focused and cost-effective follow-up and long-term management.

WHO grade, proliferation index, and progesterone receptor expression are different according to the location of meningioma.

BACKGROUND: Meningiomas may show a different WHO grade and variable biological and clinical behaviors. The aim of the present study is to assess whether WHO grade, proliferation index, progesterone receptor (PR) expression, histological subtype, neuroradiological features, and the recurrence rate differ depending on the tumor location. METHODS: Three hundred meningiomas operated on from 2006 to 2016 were reviewed. The WHO grade (2007 classification), Ki67-MIB1, progesterone receptor expression, and histological subtype were reexamined and correlated to the meningioma location, classified as medial skull base, lateral skull base, non-skull base, and spinal. RESULTS: Non-skull base and lateral skull base meningiomas showed significantly higher rates of atypical WHO II forms (34% and 25.5% respectively) than medial skull base (12.5%) and spinal ones (7%) (p = 0.0003) and also higher rates of tumors with Ki67-Li > 4% (42% and 38% vs 22% and 14%) (p = 0.0031). The rate of meningiomas with PR expression ≤ 50% was significantly lower in medial skull base (25%) than in non-skull base (48%) (p = 0.009). Meningothelial and transitional meningiomas were more frequent at the skull base (68.5% and 54.5%, respectively), the fibroblastic subtype at the non-skull base (48.5%), and the psammomatous at the spinal canal (50%) (p < 0.00001). Medial skull base and spinal meningiomas showed significantly lower size (p < 0.00001), lower rates of cases with lost arachnoid interface (p = 0.0022), and significantly lower recurrence rates (p = 0.0035) than lateral skull base and non-skull base meningiomas. CONCLUSION: Medial skull base meningiomas show lower size, lower rate of atypical forms, lower Ki67-Li values, and significantly higher PR expression than those at the lateral skull base and non-skull base. This corresponds to lesser aggressiveness and lower recurrence rates.

Anti-Apoptotic and Anti-Oxidant Proteins in Glioblastomas: Immunohistochemical Expression of Beclin and DJ-1 and Its Correlation with Prognosis.

DJ-1 deglycase is a protein with anti-oxidative and anti-apoptotic properties and its role in oncogenesis is controversial. Indeed in primary breast cancer and non-small-cell lung carcinoma, its higher expression was shown in more aggressive tumors while in other neoplasms (e.g., pancreatic adenocarcinoma), higher expression was related to better prognosis. Beclin has a relevant role in autophagy and cellular death regulation, processes that are well known to be impaired in neoplastic cells. DJ-1 shows the ability to modulate signal transduction. It can modulate autophagy through many signaling pathways, a process that can mediate either cell survival or cell death depending on the circumstances. Previously, it has been suggested that the involvement of DJ-1 in autophagy regulation may play a role in tumorigenesis. The aim of our study was to investigate the link between DJ-1 and Beclin-1 in glioblastoma through the immunohistochemical expression of such proteins and to correlate the data obtained with prognosis. Protein expression was assessed by immunohistochemistry and the immunoscores were correlated with clinicopathologic parameters. Kaplan-Meier survival curves were generated. A statistically significant association between DJ-1 score and recurrence (p = 0.0189) and between the former and Isocitrate Dehydrogenase 1 (IDH1) mutation (p = 0.0072) was observed. Kaplan-Meier survival curve analysis revealed that a higher DJ-1 score was associated with longer overall survival (p = 0.0253, ĸ2 = 5.005). Furthermore, an unexpected direct correlation (p = 0.0424, r = 0.4009) between DJ-1 and Beclin score was evident. The most significant result of the present study was the evidence of high DJ-1 expression in IDH-mutant tumors and in cases with longer overall survival. This finding could aid, together with IDH1, in the identification of glioblastomas with better prognosis.

ATM and p53 combined analysis predicts survival in glioblastoma multiforme patients: A clinicopathologic study.

Glioblastoma is one of the most malignant cancers, with a distinguishing dismal prognosis: surgery followed by chemo- and radiotherapy represents the current standard of care, and chemo- and radioresistance underlie disease recurrence and short overall survival of patients suffering from this malignancy. ATM is a kinase activated by autophosphorylation upon DNA doublestrand breaks arising from errors during replication, byproducts of metabolism, chemotherapy or ionizing radiations; TP53 is one of the most popular tumor suppressor, with a preeminent role in DNA damage response and repair. To study the effects of the immunohistochemical expression of p-ATM and p53 in glioblastoma patients, 21 cases were retrospectively examined. In normal brain tissue, p-ATM was expressed only in neurons; conversely, in tumors cells, the protein showed a variable cytoplasmic expression (score: +,++,+++), with being completely undetectable in three cases. Statistical analysis revealed that high p-ATM score (++/+++) strongly correlated to shorter survival (P = 0.022). No difference in overall survival was registered between p53 normally expressed (NE) and overexpressed (OE) glioblastoma patients (P = 0.669). Survival analysis performed on the results from combined assessment of the two proteins showed that patients with NE p53 /low pATM score had longer overall survival than the NE p53/ high pATM score counterpart. Cox-regression analysis confirmed this finding (HR = 0.025; CI 95% = 0.002-0.284; P = 0.003). Our study outlined the immunohistochemical expression of p-ATM/p53 in glioblastomas and provided data on their possible prognostic/predictive of response role. A "non-oncogene addiction" to ATM for NEp53 glioblastoma could be postulated, strengthening the rationale for development of ATM inhibiting drugs.

Role of Macrophages in Brain Tumor Growth and Progression.

The role of macrophages in the growth and the progression of tumors has been extensively studied in recent years. A large body of data demonstrates that macrophage polarization plays an essential role in the growth and progression of brain tumors, such as gliomas, meningiomas, and medulloblastomas. The brain neoplasm cells have the ability to influence the polarization state of the tumor associated macrophages. In turn, innate immunity cells have a decisive role through regulation of the acquired immune response, but also through humoral cross-talking with cancer cells in the tumor microenvironment. Neoangiogenesis, which is an essential element in glial tumor progression, is even regulated by the tumor associated macrophages, whose activity is linked to other factors, such as hypoxia. In addition, macrophages play a decisive role in establishing the entry into the bloodstream of cancer cells. As is well known, the latter phenomenon is also present in brain tumors, even if they only rarely metastasize. Looking ahead in the future, we can imagine that characterizing the relationships between tumor and tumor associated macrophage, as well as the study of circulating tumor cells, could give us useful tools in prognostic evaluation and therapy. More generally, the study of innate immunity in brain tumors can boost the development of new forms of immunotherapy.

Evaluation of matrix metalloproteinase type IV-collagenases in serum of patients with tumors of the central nervous system.

The basement membrane collagen IV-degrading matrix metalloproteinases -2 and -9 (MMPs) are most often linked to the malignant phenotype of tumor cells by playing a critical role in invasion, metastasis, angiogenesis, and vasculogenesis. We verified the activity of these two MMPs in the sera of patients affected by brain tumors (20 gliomas, 28 meningiomas and 20 metastasis) by zymography. The sera of 25 healthy volunteers with no concomitant illnesses were used for controls. Zymography showed four dominant gelatinolytic bands of 240, 130, 92 (MMP-9) and 72 (MMP-2) kDa. No statistically significant variations of MMP-2 proteolytic activity between patients and healthy individuals were observed. On the contrary, MMP-9 (both monomeric and multimeric forms) lytic activities were significantly higher in tumors specimens compared to healthy controls (p < 0.001). Moreover, MMP-9 immunohistochemistry revealed: (1) a strong reactivity in neoplastic vessels of high-grade gliomas showing an inverse correlation with serum multimeric gelatinolytic activity; (2) a cytoplasmatic reactivity in meningiomas with a significantly increase in atypical meningioma compared with low-grade ones (p = 0.036); (3) a positive correlation between MMP-9 and Ki-67 (Sperman Rho coefficient r = 0.418 and p = 0.034). Our results suggest that serum and tissue MMP-9 might provide clinicians additional objective information in intracranial neoplasms. Finally, it should be possible to use MMP-9 as a target for new forms of therapy. Nevertheless, due to the small number of patients included in the study, the conclusion may not be transferable to the general population and therefore further evaluations are needed.

Atypical pituitary adenomas: clinical characteristics and role of ki-67 and p53 in prognostic and therapeutic evaluation. A series of 50 patients.

The aim of the study was to assess incidence rate, hormonal activity, and local invasiveness and evaluate outcomes of so-diagnosed atypical pituitary adenomas that underwent endoscopic endonasal surgery at the Division of Neurosurgery of Università degli Studi di Napoli Federico II. According to the 2004 WHO classification, atypical pituitary adenomas are defined by an invasive growth, Ki-67/MIB-1 proliferative index greater than 3 %, high p53 immunoreactivity, and increased mitotic activity. A retrospective analysis of a series of 434 pituitary adenomas that underwent endoscopic endonasal surgery at our department between March 2007 and February 2013 was performed. Fifty adenomas (11.5 %) met the criteria of diagnosis of atypical lesions; 10 (21.6 %) of the 50 patients were recurrent tumors with a previous transsphenoidal surgery. Forty-one (82 %) were macroadenomas, and 21/50 (42 %) showed a clear invasion of the cavernous sinus. Histotype of atypical adenomas figured out to be nonfunctioning in 23 cases (46 %), PRL secreting in 10 cases (20 %), ACTH secreting and GH secreting each apart in 8 patients (16 %), and in a single case a GH/PRL secreting adenoma (2 %). The Ki-67 labeling index ranged from 3.5 to 22.5 % (mean 5.6 %). Tumor recurrence was observed in six cases (12 %) after a mean time of 18 months (range 9-24 months). Mean follow-up was 36.5 months (range 2-80 months). Atypical pituitary adenomas account for ca. 10 % of all pituitary adenomas; these lesions have peculiar features. It should be considered that a strong immunopositivity of p53 and higher Ki-67 LI could predict an increased risk of tumor recurrence, but more studies and larger series are expected to confirm and enlarge the diagnostic and therapeutic management process of these lesions.

Expression of p40 (∆Np63) protein in meningiomas, an unexpected finding: immunohistochemical study and evaluation of its possible prognostic role.

According to the 2007 WHO (World Health Organization) Classification, meningiomas are divided into three grades of malignancy, with different recurrence rate, based exclusively on histopathological parameters. Loss/reduction of PgR (Progesterone Receptor) expression and increased Ki67 L.I. (Labeling Index) have been proven as possible prognostic factors able to predict the relapse of the disease. However, they sometimes result unreliable, especially when discordant. p40 is the short form of the p53 homologue gene p63, also named ∆Np63, and its antibody has recently been introduced as a highly specific diagnostic marker of the squamous cell carcinoma of the lung. Nevertheless its expression has been found in many other unconventional sites (e.g. placenta, urotheluim, etc). Herein we assessed the immuno-expression of p40 protein in a series of 72 meningiomas (35 grade I and 37 grade II) and analyzed its correlation with clinicopathological parameters, overall survival and recurrence free interval. We found that a high p40 score correlated with high histological grade, presence of recurrence, increased Ki67 L.I. and loss/reduction of PgR signal. Moreover, a higher expression of p40 was shown to be a significant prognostic factor for the development of recurrences and resulted a prognostic independent variable in multivariate analysis. Overall, for the first time, we investigated the expression of p40 protein in meningiomas and explored its usefulness as prognostic marker in addition to PgR and Ki67 L.I.

Essential role of ultrastructural examination for spindle cell oncocytoma: Case report of a rare neoplasm and review of the literature.

Spindle cell oncocytoma (SCO) is an extremely rare neoplasm of the sellar region recognized as a distinct benign histopathological subtype of pituitary tumors in the 2007 World Health Organization classification of tumors of the central nervous system. The morphology of its neoplastic cells (spindle cells and granular eosinophilic cytoplasm) is common to several other lesions so that immunohistochemistry, together with ultrastructural examination, becomes essential in solving this differential diagnosis. Despite being labeled as benign, recurrence is described. Herein, we report a case of SCO in a 77-year-old man and discuss the diagnostic difficulties, ultrastructural aspects, and prognostic factors.

Comparison of Left Ventricular Myocardial Structure and Function in Patients with Aortic Stenosis and Those with Pure Aortic Regurgitation.

OBJECTIVE: We aimed to support the structural and functional distinction between aortic stenosis (AS) and aortic regurgitation (AR). METHODS: Biopsy specimens taken from 70 selected patients (35 with AS and 35 with AR) undergoing aortic valve replacement (AVR) were analyzed for their cardiomyocyte dimensions and structure, interstitial fibrosis and contractile function. To determine normal values of contractile function, 10 donor hearts were analyzed. RESULTS: Cardiomyocyte diameter was higher in AS than in AR (22.7 ± 2.2 vs. 13.2 ± 0.7 µm, p < 0.001). Length was higher in AR (121.2 ± 9.4 vs. 95.6 ± 3.7 µm, p < 0.001). Collagen volume fraction was increased in both AS and AR, but was lower in the AS specimens (7.7 ± 2.3 vs. 8.9 ± 2.3, p = 0.01). Myofibril density was reduced in AR (38 ± 4 vs. 48 ± 5%, p < 0.001). Cardiomyocyte diameter and length were closely linked to the relative left ventricular (LV) wall thickness (R2 = 0.85, p < 0.001 and R2 = 0.68, p = 0.003). The cardiomyocytes of AS patients had higher Fpassive (6.6 ± 0.3 vs. 4.6 ± 0.2 kN/m2, p < 0.001), but their total force was comparable. Fpassive was also significantly higher in AS patients with restrictive rather than pseudo-normal LV filling (7.3 ± 0.5 vs. 6.7 ± 0.6, p = 0.004). In AS patients, but not in AR patients, Fpassive showed a significant association with the cardiomyocyte diameter (R2 = 0.88, p < 0.001 vs. R2 = 0.31, p = 0.6). CONCLUSIONS: LV myocardial structure and function differ in AS and AR, allowing for compensative adjustment of the diastolic/systolic properties of the myocardium. © 2015 S. Karger AG, Basel.