Metastatic Uterine Leiomyosarcoma in the Upper Buccal Gingiva Misdiagnosed as an Epulis

Uterine leiomyosarcoma (LMS) is a rare tumor constituting 1% of all uterine malignancies. This sarcoma demonstrates an aggressive growth pattern with an high rate of recurrence with hematologic dissemination; the most common sites are lung, liver, and peritoneal cavity, head and neck district being rarely interested. Only other four cases of metastasis in the oral cavity have been previously described. The treatment of choice is surgery and the use of adjuvant chemotherapy and radiation has limited impact on clinical outcome. In case of metastases, surgical excision can be performed considering extent of disease, number and type of distant lesions, disease free interval from the initial diagnosis to the time of metastases, and expected life span. We illustrate a case of uterine LMS metastasis in the upper buccal gingiva that occurred during chemotherapy in a 63-year-old woman that underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy for a diagnosis of LMS staged as pT2bN0 and that developed lung metastases eight months after primary treatment. Surgical excision of the oral mass (previously misdiagnosed as epulis at a dental center) and contemporary reconstruction with pedicled temporalis muscle flap was performed in order to improve quality of life. Even if resection was achieved in free margins, "local" relapse was observed 5 months after surgery

From Uterus to Brain: An Update on Epidemiology, Clinical Features, and Treatment of Brain Metastases From Gestational Trophoblastic Neoplasia

In this review, we provide the state of the art about brain metastases (BMs) from gestational trophoblastic neoplasia (GTN), a rare condition. Data concerning the epidemiology, clinical presentation, innovations in therapeutic modalities, and outcomes of GTN BMs are comprehensively presented with particular attention to the role of radiotherapy, neurosurgery, and the most recent chemotherapy regimens. Good response rates have been achieved thanks to multi-agent chemotherapy, but brain involvement by GTNs entails significant risks for patients’ health since sudden and extensive intracranial hemorrhages are possible. Moreover, despite the evolution of treatment protocols, a small proportion of these patients ultimately develops a resistant disease. To tackle this unmet clinical need, immunotherapy has been recently proposed. The role of this novel option for this subset of patients as well as the achieved results so far are also discussed

Validation of Androgen Receptor loss as a risk factor for the development of brain metastases from ovarian cancers

Abstract Background Central nervous system (CNS) spreading from epithelial ovarian carcinoma (EOC) is an uncommon but increasing phenomenon. We previously reported in a small series of 11 patients a correlation between Androgen Receptor (AR) loss and localization to CNS. Aims of this study were: to confirm a predictive role of AR loss in an independent validation cohort; to evaluate if AR status impacts on EOC survival. Results We collected an additional 29 cases and 19 controls as validation cohort. In this independent cohort at univariate analysis, cases exhibited lower expression of AR, considered both as continuous (p <  0.001) and as discrete variable (10% cut-off: p <  0.003; Immunoreactive score: p <  0.001). AR negative EOC showed an odds ratio (OR) = 8.33 for CNS dissemination compared with AR positive EOC. Kaplan-Meier curves of the combined dataset, combining data of new validation cohort with the previously published cohort, showed that AR <  10% significantly correlates with worse outcomes (p = 0.005 for Progression Free Survival (PFS) and p = 0.002 for brain PFS (bPFS) respectively). Comparison of AR expression between primary tissue and paired brain metastases in the combined dataset did not show any statistically significant difference. Conclusions We confirmed AR loss as predictive role for CNS involvement from EOC in an independent cohort of cases and controls. Early assessment of AR status could improve clinical management and patients’ prognosis

A complex of α(6) integrin and E-cadherin drives liver metastasis of colorectal cancer cells through hepatic angiopoietin-like 6.

Homing of colorectal cancer (CRC) cells to the liver is a non-random process driven by a crosstalk between tumour cells and components of the host tissue. Here we report the isolation of a liver metastasis-specific peptide ligand (CGIYRLRSC) that binds a complex of E-cadherin and α(6) integrin on the surface of CRC cells. We identify angiopoietin-like 6 protein as a peptide-mimicked natural ligand enriched in hepatic blood vessels of CRC patients. We demonstrate that an interaction between hepatic angiopoietin-like 6 and tumoural α(6) integrin/E-cadherin drives liver homing and colonization by CRC cells, and that CGIYRLRSC inhibits liver metastasis through interference with this ligand/receptor system. Our results indicate a mechanism for metastasis whereby a soluble factor accumulated in normal vessels functions as a specific ligand for circulating cancer cells. Consistently, we show that high amounts of coexpressed α(6) integrin and E-cadherin in primary tumours represent a poor prognostic factor for patients with advanced CRC

Polymorphisms of genes coding for ghrelin and its receptor in relation to colorectal cancer risk: a two-step gene-wide case-control study

<p>Abstract</p> <p>Background</p> <p>Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor (GHSR), has two major functions: the stimulation of the growth hormone production and the stimulation of food intake. Accumulating evidence also indicates a role of ghrelin in cancer development.</p> <p>Methods</p> <p>We conducted a case-control study to examine the association of common genetic variants in the genes coding for ghrelin (GHRL) and its receptor (GHSR) with colorectal cancer risk. Pairwise tagging was used to select the 11 polymorphisms included in the study. The selected polymorphisms were genotyped in 680 cases and 593 controls from the Czech Republic.</p> <p>Results</p> <p>We found two SNPs associated with lower risk of colorectal cancer, namely SNPs rs27647 and rs35683. We replicated the two hits, in additional 569 cases and 726 controls from Germany.</p> <p>Conclusion</p> <p>A joint analysis of the two populations indicated that the T allele of rs27647 SNP exerted a protective borderline effect (P_trend= 0.004).</p

Contemporary management of primary parapharyngeal space tumors

The parapharyngeal space is a complex anatomical area. Primary parapharyngeal tumors are rare tumors and 80% of them are benign. A variety of tumor types can develop in this location; most common are salivary gland neoplasm and neurogenic tumors. The management of these tumors has improved greatly owing to the developments in imaging techniques, surgery, and radiotherapy. Most tumors can be removed with a low rate of complications and recurrence. The transcervical approach is the most frequently used. In some cases, minimally invasive approaches may be used alone or in combination with a limited transcervical route, allowing large tumors to be removed by reducing morbidity of expanded approaches. An adequate knowledge of the anatomy and a careful surgical plan is essential to tailor management according to the patient and the tumor. The purpose of the present review was to update current aspects of knowledge related to this more challenging area of tumor occurrence.Peer reviewe

Cancers of unknown primary origin: current perspectives and future therapeutic strategies

It is widely accepted that systemic neoplastic spread is a late event in tumour progression. However, sometimes, rapidly invasive cancers are diagnosed because of appearance of metastatic lesions in absence of a clearly detectable primary mass. This kind of disease is referred to as cancer of unknown primary (CUP) origin and accounts for 3-5% of all cancer diagnosis. There is poor consensus on the extent of diagnostic and pathologic evaluations required for these enigmatic cases which still lack effective treatment. Although technology to predict the primary tumour site of origin is improving rapidly, the key issue is concerning the biology which drives early occult metastatic spreading. This review provides the state of the art about clinical and therapeutic management of this malignant syndrome; main interest is addressed to the most recent improvements in CUP molecular biology and pathology, which will lead to successful tailored therapeutic options

Update on HHV-8-Associated Malignancies

The human herpesvirus 8 (HHV-8) is the oncogenic virus associated with Kaposi’s sarcoma (KS) and lymphoproliferative disorders, namely, primary effusion lymphoma and multicentric Castleman’s disease. KS is among the most common malignancies seen in HIV-infected patients despite the decreased incidence of KS in the era of highly active antiretroviral therapy. Advances in molecular pathology reveal HHV-8 tumorigenesis is mediated through molecular mimicry wherein viral-encoded proteins can activate several cellular signaling cascades while evading immune surveillance. This knowledge has led to the evolution of multiple therapeutic strategies against specific molecular targets. Many such therapeutic modalities have shown activity, but none have proven to be curative. Identifying possible prognostic factors is another active area of research. This review summarizes the recent developments in the fields of virus transmission, molecular biology, and treatment of HHV-8-related neoplasms

A comprehensive PDX gastric cancer collection captures cancer cell–intrinsic transcriptional MSI traits

Gastric cancer is the world's third leading cause of cancer mortality. In spite of significant therapeutic improvements, the clinical outcome for patients with advanced gastric cancer is poor; thus, the identification and validation of novel targets is extremely important from a clinical point of view. We generated a wide, multilevel platform of gastric cancer models, comprising 100 patient-derived xenografts (PDX), primary cell lines, and organoids. Samples were classified according to their histology, microsatellite stability, Epstein–Barr virus status, and molecular profile. This PDX platform is the widest in an academic institution, and it includes all the gastric cancer histologic and molecular types identified by The Cancer Genome Atlas. PDX histopathologic features were consistent with those of patients' primary tumors and were maintained throughout passages in mice. Factors modulating grafting rate were histology, TNM stage, copy number gain of tyrosine kinases/KRAS genes, and microsatellite stability status. PDX and PDX-derived cells/organoids demonstrated potential usefulness to study targeted therapy response. Finally, PDX transcriptomic analysis identified a cancer cell–intrinsic microsatellite instability (MSI) signature, which was efficiently exported to gastric cancer, allowing the identification, among microsatellite stable (MSS) patients, of a subset of MSI-like tumors with common molecular aspects and significant better prognosis. In conclusion, we generated a wide gastric cancer PDX platform, whose exploitation will help identify and validate novel "druggable" targets and optimize therapeutic strategies. Moreover, transcriptomic analysis of gastric cancer PDXs allowed the identification of a cancer cell–intrinsic MSI signature, recognizing a subset of MSS patients with MSI transcriptional traits, endowed with better prognosis