On a Rare Cutaneous Metastasis from a Sacrococcygeal Chordoma

Chordomas are rare malignant tumors of notochordal origin and are rare locally aggressive ones with a metastatic potential. The skin rarely is seen as metastatic site. We describe a case of an adult woman with cutaneous metastasis of a primary sacral chordoma excised ten years before, which appeared as a painless cutaneous mass located in the dorsal region. Once removed, the surgical specimen was formalin fixed and in paraffin embedded. Sections were stained with haematoxylin-eosin, and histochemical and immunohistochemical investigations were performed. Histologically, the neoplasia was characterized by cords or single tumor cells with an abundant myxoid stroma, conspicuous pale vacuolated cytoplasm (the classic "physaliphorous cells"), and mild nuclear atypia. Mitotic activity was scanty. At immunohistochemistry, the tumor cells were diffusely positive for S-100 protein, pan-keratins, EMA, and vimentin. A diagnosis of cutaneous metastasis of chordoma was performed. This case illustrates a diagnostic challenge because of the unusual presentation of an already rare tumor

An Autochthonous Outbreak of the SARS-CoV-2 P.1 Variant of Concern in Southern Italy, April 2021

The SARS-CoV-2 P.1 variant of concern (VOC) was first identified in Brazil and is now spreading in European countries. It is characterized by the E484K mutation in the receptor-binding domain, which could contribute to the evasion from neutralizing antibodies. In Italy, this variant was first identified in January 2021. Here, we report an autochthonous outbreak of SARS-CoV-2 P.1 variant infections in southern Italy in subjects who had not travelled to endemic areas or outside the Apulia region. The outbreak involved seven subjects, three of whom had received a COVID-19 vaccine (one had received two doses and two had received one dose). Four patients had a mild clinical presentation. Laboratory investigations of nasopharyngeal swabs revealed that all strains were S-gene target failure-negative and molecular tests revealed they were the P.1 variant. Whole-genome sequencing confirmed that five subjects were infected with closely related strains classified as the P.1 lineage. The circulation of VOCs highlights the importance of strictly monitoring the spread of SARS-CoV-2 variants through genomic surveillance and of investigating local outbreaks. Furthermore, public health measures including social distancing, screening, and quarantine for travelers are key tools to slow down the viral transmission and to contain and mitigate the impact of VOC diffusion, and rapid scaling-up of vaccination is crucial to avoid a possible new epidemic wave

Mitofusin-2 Down-Regulation Predicts Progression of Non-Muscle Invasive Bladder Cancer

Identification of markers predicting disease outcome is a major clinical issue for non-muscle invasive bladder cancer (NMIBC). The present study aimed to determine the role of the mitochondrial proteins Mitofusin-2 (Mfn2) and caseinolytic protease P (ClpP) in predicting the outcome of NMIBC. The study population consisted of patients scheduled for transurethral resection of bladder tumor upon the clinical diagnosis of bladder cancer (BC). Samples of the main bladder tumor and healthy-looking bladder wall from patients classified as NMIBC were tested for Mfn2 and ClpP. The expression levels of these proteins were correlated to disease recurrence, progression. Mfn2 and ClpP expression levels were significantly higher in lesional than in non-lesional tissue. Low-risk NMIBC had significantly higher Mfn2 expression levels and significantly lower ClpP expression levels than high-risk NMIBC; there were no differences in non-lesional levels of the two proteins. Lesional Mfn2 expression levels were significantly lower in patients who progressed whereas ClpP levels had no impact on any survival outcome. Multivariable analysis adjusting for the EORTC scores showed that Mfn2 downregulation was significantly associated with disease progression. In conclusion, Mfn2 and ClpP proteins were found to be overexpressed in BC as compared to non-lesional bladder tissue and Mfn2 expression predicted disease progression

On a Rare Cutaneous Metastasis from a Sacrococcygeal Chordoma

Chordomas are rare malignant tumors of notochordal origin and are rare locally aggressive ones with a metastatic potential. The skin rarely is seen as metastatic site. We describe a case of an adult woman with cutaneous metastasis of a primary sacral chordoma excised ten years before, which appeared as a painless cutaneous mass located in the dorsal region. Once removed, the surgical specimen was formalin fixed and in paraffin embedded. Sections were stained with haematoxylin-eosin, and histochemical and immunohistochemical investigations were performed. Histologically, the neoplasia was characterized by cords or single tumor cells with an abundant myxoid stroma, conspicuous pale vacuolated cytoplasm (the classic “physaliphorous cells”), and mild nuclear atypia. Mitotic activity was scanty. At immunohistochemistry, the tumor cells were diffusely positive for S-100 protein, pan-keratins, EMA, and vimentin. A diagnosis of cutaneous metastasis of chordoma was performed. This case illustrates a diagnostic challenge because of the unusual presentation of an already rare tumor

Gliomatosis cerebri type II: two case reports

Two types of gliomatosis cerebri exist: Type I and Type II. We report the results of a histological and genetic study of two cases of gliomatosis cerebri Type II, correlating these results with therapy and prognosis. Case presentation Two patients, a 52-year-old man (Patient 1) and a 76-year-old man (Patient 2) with gliomatosis cerebri II were admitted to our institution; they underwent surgical treatment and received radiotherapy and chemotherapy. At the 24-month follow-up, Patient 1 was still alive, while Patient 2 had died. The poor prognosis of Patient 2 was underlined by molecular analysis which showed that the angiogenesis related genes VCAM1 and VEGF were overexpressed, reflecting the high degree of neovascularization. Conclusion Genes involved in drug resistance and metallothioneins were highly expressed in Patient 2 and this, associated with unmethylated O6-methylguanine methyltransferase, can explain the lack of response to chemotherapy

Modulation of complement activation by pentraxin-3 in prostate cancer.

Pentraxin 3 (PTX3) is an essential component of the innate immune system and a recognized modulator of Complement cascade. The role of Complement system in the pathogenesis of prostate cancer has been largely underestimated. The aim of our study was to investigate the role of PTX3 as possible modulator of Complement activation in the development of this neoplasia. We performed a single center cohort study; from January 2017 through December 2018, serum and prostate tissue samples were obtained from 620 patients undergoing prostate biopsy. A group of patients with benign prostatic hyperplasia (BPH) underwent a second biopsy within 12-36 months demonstrating the presence of a prostate cancer (Group A, n = 40) or confirming the diagnosis of BPH (Group B, N = 40). We measured tissue PTX3 protein expression together with complement activation by confocal microscopy in the first and second biopsy in group A and B patients. We confirmed that that PTX3 tissue expression in the first biopsy was increased in group A compared to group B patients. C1q deposits were extensively present in group A patients co-localizing and significantly correlating with PTX3 deposits; on the contrary, C1q/PTX3 deposits were negative in group B. Moreover, we found a significantly increased expression of C3a and C5a receptors within resident cells in group A patient. Interestingly, C1q/PTX3 deposits were not associated with activation of the terminal Complement complex C5b-9; moreover, we found a significant increase of Complement inhibitor CD59 in cancer tissue. Our data indicate that PTX3 might play a significant pathogenic role in the development of this neoplasia through recruitment of the early components of Complement cascade with hampered activation of terminal Complement pathway associated with the upregulation of CD59. This alteration might lead to the PTX3-mediated promotion of cellular proliferation, angiogenesis and insensitivity to apoptosis possible leading to cancer cell invasion and migration

Development and Internal Validation of Novel Nomograms Based on Benign Prostatic Obstruction-Related Parameters to Predict the Risk of Prostate Cancer at First Prostate Biopsy

The present study aimed to determine the ability of novel nomograms based onto readily-available clinical parameters, like those related to benign prostatic obstruction (BPO), in predicting the outcome of first prostate biopsy (PBx). To do so, we analyzed our Internal Review Board-approved prospectively-maintained PBx database. Patients with PSA>20 ng/ml were excluded because of their high risk of harboring prostate cancer (PCa). A total of 2577 were found to be eligible for study analyses. The ability of age, PSA, digital rectal examination (DRE), prostate volume (PVol), post-void residual urinary volume (PVR), and peak flow rate (PFR) in predicting PCa and clinically-significant PCa (CSPCa)was tested by univariable and multivariable logistic regression analysis. The predictive accuracy of the multivariate models was assessed using receiver operator characteristic curves analysis, calibration plot, and decision-curve analyses (DCA). Nomograms predicting PCa and CSPCa were built using the coefficients of the logit function. Multivariable logistic regression analysis showed that all variables but PFR significantly predicted PCA and CSPCa. The addition of the BPO-related variables PVol and PVR to a model based on age, PSA and DRE findings increased the model predictive accuracy from 0.664 to 0.768 for PCa and from 0.7365 to 0.8002 for CSPCa. Calibration plot demonstrated excellent models' concordance. DCA demonstrated that the model predicting PCa is of value between ~15 and ~80% threshold probabilities, whereas the one predicting CSPCa is of value between ~10 and ~60% threshold probabilities. In conclusion, our novel nomograms including PVR and PVol significantly increased the accuracy of the model based on age, PSA and DRE in predicting PCa and CSPCa at first PBx. Being based onto parameters commonly assessed in the initial evaluation of men “prostate health,” these novel nomograms could represent a valuable and easy-to-use tool for physicians to help patients to understand their risk of harboring PCa and CSPCa

Radiation-induced haemorrhagic cystitis after prostate cancer radiotherapy : factors associated to hospitalization and treatment strategies

Late onset of radiation-induced haemorrhagic cystitis (RHC) after radiation therapy (RT) for prostate cancer (PCa) may present or evolve severely, requiring hospitalization with invasive interventions. In the present study, we have analysed the prevalence and risk factors associated with the onset of RHC. From January 2002 to May 2017, 1421 patients undertook RT for PCa as a primary, adjuvant, or salvage treatment option. RHC presented in 5.6% (n = 80) of the patients; the diagnosis was based on clinical and endoscopic characteristics. Variables in observation included patients, tumours, and RT-dosimetry characteristics. Patients with a previous history of bladder cancer were excluded. Univariate (Student t /Chi square) and uni-/multivariate Cox regression analysis were performed; the events and time-points were hospitalization and time-to-event, respectively. There were 80 patients with a mean age at RT of 70.1 years (SD 6.4), mean time lag to RHC of 43.9 months (SD 37.5). Median Emergency attendance was two and three times for patients without/with hospitalization, respectively. There were in total 64 admissions with invasive treatment required in 26/36 (72.2%) of the patients hospitalised, including transurethral fulguration in 22 and radical cystectomy in 5. Patients at higher risk of hospitalization were those undertaking antiplatelet/anticoagulant treatment (HR:3.30; CI 95%:1.53-3.30; p = 0.002) and those treated with salvage RT with higher bladder volume receiving >70 Gy (bladder V70) (HR:1.03; CI 95%:1.01-1.05; p = 0.027). At receiving operating characteristic analysis, the cutoff for bladder V70 was 29%. Nearly half of patients presenting RHC may require invasive treatment including cystectomy. Risk factors associated with hospitalization are patients undertaking antiplatelet/coagulant treatment and bladder V70 > 29% in salvage RT patients

T-Cell Lymphoblastic Lymphoma Arising in the Setting of Myeloid/Lymphoid Neoplasms with Eosinophilia: LMO2 Immunohistochemistry as a Potentially Useful Diagnostic Marker

Simple Summary Rarely, T-lymphoblastic lymphoma (T-LBL) may develop in the setting of myeloid/lymphoid neoplasms with eosinophilia. Given important therapeutic implications, it is crucial to identify T-LBL arising in this particular context. LIM domain only 2 (LMO2) is known to be overexpressed in almost all sporadic T-LBL and not in immature TdT-positive T-cells in the thymus and in indolent T-lymphoblastic proliferations. We retrospectively evaluated the clinical, morphological, immunohistochemical and molecular features of 11 cases of T-LBL occurring in the setting of myeloid/lymphoid neoplasms with eosinophilia and investigated the immunohistochemical expression of LMO2 in this setting of T-LBL. Interestingly, 9/11 cases were LMO2 negative, with only 2 cases showing partial expression. In our study, we would suggest that LMO2 immunostaining, as part of the diagnostic panel for T-LBL, may represent a useful marker to identify T-LBL developing in the context of myeloid/lymphoid neoplasms with eosinophilia. Background: Rarely, T-lymphoblastic lymphoma (T-LBL) may develop in the setting of myeloid/lymphoid neoplasms with eosinophilia (M/LNs-Eo), a group of diseases with gene fusion resulting in overexpression of an aberrant tyrosine kinase or cytokine receptor. The correct identification of this category has relevant therapeutic implications. LIM domain only 2 (LMO2) is overexpressed in most T-LBL, but not in immature TdT-positive T-cells in the thymus and in indolent T-lymphoblastic proliferations (iT-LBP). Methods and Results: We retrospectively evaluated 11 cases of T-LBL occurring in the context of M/LNs-Eo. Clinical, histological, immunohistochemical and molecular features were collected and LMO2 immunohistochemical staining was performed. The critical re-evaluation of these cases confirmed the diagnosis of T-LBL with morphological, immunohistochemical and molecular features consistent with T-LBL occurring in M/LNs-Eo. Interestingly, LMO2 immunohistochemical analysis was negative in 9/11 cases, whereas only 2 cases revealed a partial LMO2 expression with a moderate and low degree of intensity, respectively. Conclusions: LMO2 may represent a potentially useful marker to identify T-LBL developing in the context of M/LNs-Eo. In this setting, T-LBL shows LMO2 immunohistochemical profile overlapping with cortical thymocytes and iT-LBP, possibly reflecting different molecular patterns involved in the pathogenesis of T-LBL arising in the setting of M/LNs-Eo

Epigenetic fingerprint in endometrial carcinogenesis: the hypothesis of a uterine field cancerization.

"Abstract. Transcriptional silencing by CpG island hypermethylation plays a critical role in endometrial carcinogenesis. In a collection of benign, premalignant and malignant endometrial lesions, a methylation profile of a complete gene panel, such steroid receptors (ERα, PR), DNA mismatch repair (hMLH1), tumor-suppressor genes (CDKN2A\/P16 and CDH1\/E-CADHERIN) and WNT pathway inhibitors (SFRP1, SFRP2, SFRP4, SFRP5) was investigated in order to demonstrate their pathogenetic role in endometrial lesions. Our results indicate that gene hypermethylation may be an early event in endometrial endometrioid tumorigenesis. Particularly, ERα, PR, hMLH1, CDKN2A\/P16, SFRP1, SFRP2 and SFRP5 revealed a promoter methylation status in endometrioid carcinoma, whereas SFRP4 showed demethylation in cancer. P53 immunostaining showed weak-focal protein expression level both in hyperplasic lesions and in endometrioid cancer. Non-endometrioid cancers showed very low levels of epigenetic methylations, but strong P53 protein positivity. Fisher exact test revealed a statistically significant association between hMLH1, CDKN2A\/P16 and SFRP1 genes methylation and endometrioid carcinomas and between hMLH1 gene methylation and peritumoral endometrium (p < 0.05). Our data confirm that the methylation profile of the peritumoral endometrium is different from the altered molecular background of benign endometrial polyps and hyperplasias. Therefore, our findings suggest that the methylation of hMLH1, CDKN2A\/P16 and SFRP1 may clearly distinguish between benign and malignant lesions. Finally, this study assessed that the use of an epigenetic fingerprint may improve the current diagnostic tools for a better clinical management of endometrial lesions.