The association of gastrointestinal stromal tumor (GIST), synchronous or metachronous with other tumors is reported in special literature, the most frequent being associated with other gastrointestinal tumors. GISTs are the most common mesenchymal neoplasm of the gastro-intestinal tract with a malignant potential. We present a case of 68-year-old male patient diagnosed with GIST stage IV, unreachable due to liver metastases, treated with Imatinib, diagnosed at 13 months of prostate adenocarcinoma diagnosis [treated with hormonal therapy (HT) and external beam radiotherapy (EBRT)]; at 45 months from the first neoplasia diagnosis, the patient was diagnosed with the third neoplasia - lung squamous carcinoma - right inferior lobe, for which performed EBRT. The coexistence of GIST with other malignancies with different histology, remain a challenge for the clinician from etiological, and also from therapeutically actions point of view.

Cystic cervical hygroma or cervical cystic lymphangioma is a congenital benign disease of the lymphatic system that is characterized by the accumulation of lymph in the jugular lymphatic sacs of the nuchal region. The factor that causes this pathology is not clarified yet but the physiopathological mechanism seems to be multifactorial. The incidence and prevalence of cervical hygroma are increased in patients with Turner syndrome, Down syndrome, Klinefelter syndrome, Edwards syndrome, Patau syndrome, Noonan syndrome, pterygium syndrome, Cantrell pentalogy, Fryns syndrome, Apert syndrome, Pena-Shokeir syndrome and achondroplasia. The gold standard method in establishing the antenatal diagnosis is ultrasonography, a non-invasive and low-cost procedure. We report four cases of fetuses who were diagnosed antepartum with cervical hygroma in the Department of Obstetrics and Gynecology of the University Emergency Hospital in Bucharest, Romania. Two products of conception were send to the Department of Anatomy of the "Carol Davila" University of Medicine and Pharmacy, Bucharest, for an extensive morphological analysis. Cervical cystic hygroma is a congenital condition of variable expression in terms of both morphology and chronology. A complete ultrasound examination, performed by an experimented specialist in maternal-fetal medicine is essential in establishing the diagnosis of cervical hygroma. Screening for aneuploidies, between the 11th and 14th weeks of pregnancy is also mandatory due to the frequent association between cervical hygroma and congenital anomalies.

Here we present a report of 61-year-old female patient. Uterus with left appendages was removed together with clinically tagged "tumor of right ovary" and then extensively sampled and routinely processed with Hematoxylin-Eosin (HE) and some additional staining. There was discernible oviduct adherent to grayish, solid, polycyclic 22 cm in diameter focally necrotic tumor to be diagnosed high-grade conventional leiomyosarcoma FNCLCC (Fédération Nationale des Centres de Lutte Contre le Cancer) G3 pT2b, according to 7th edition pTNM, according to World Health Organization (WHO) 2013 International Classification of Diseases for Oncology (ICD-O): 8890÷3, in nearby of right oviduct. Grade of differentiation was given according to FNCLCC classification: grade 3 {point score: 6 = 1 [microscopically necrosis comprised 10% of the tumor] + 3 [high mitotic index eight mitoses÷one high-power field (HPF) in hot spots in HE slides; Ki67 labeled approximately 60% of tumor cells] + 2 [histopathological type: conventional leiomyosarcoma]}. The staging was more appropriate for pT2b (7th edition pTNM) for deeply seated sarcoma of soft tissues, in examined samples, there was no trace of microscopically evident ovarian texture) rather than pT1a for ovarian tumors. The tumor was alpha-smooth muscle actin (α-SMA)-positive. Detected epithelial membrane antigen (EMA) immuno-reactivity indicates a possible change in mesenchymal origin. Next generation sequencing revealed tumor protein p53 (TP53) mutation C275Y (7577114 C>T). Each soft tissue malignancy should be carefully reported with appropriate choice of staging and precisely graded with internationally acknowledged classification.

Bardet-Biedl syndrome (BBS) represents a rare ciliopathy recessive autosomal inherited. The main clinical features are retinal dystrophy, postaxial polydactyly, obesity, different degrees of cognitive deficit, renal impairment, hypogonadism and genital malformations. The genetic explanation consists in BBS genes mutations, which encode modified proteins, altering the function of the immotile cilia. As a multitude of BBS genes mutations were described, the phenotypic aspect of these disorders varies according to that. We present the case of a 22 years old female patient, known with BBS since the age of 11 and which was diagnosed and operated for bilateral ovarian dermoid cysts, at the age of 21. We did not find a similar case in literature, regarding the association between the two disorders. We consider that our case points towards the importance of periodic imagistic evaluations [magnetic resonance imaging (MRI), computed tomography (CT) or ultrasound] of these patients, not only clinical and biological. Usually, the moment they are diagnosed with hypogonadism or genital malformations (in childhood or adolescence), the genital evaluation is neglected thereafter. We also consider that our therapeutic approach can be helpful in other similar clinical situations. Another important conclusion is represented by the importance of genetic counseling of the relatives of a BBS patient, unfortunately insufficiently provided in our region.

Gastrointestinal stromal tumor (GIST) is a mesenchymal tumor originating from the Cajal interstitial cells, immunologically characterized by the c-kit gene. The evolution may be asymptomatic, discovered by chance during a necropsy, upper gastrointestinal endoscopy or due to complications of type-algic, occlusive or hemorrhage. We present the case of a voluminous gastric GIST complicated with serious upper gastrointestinal bleeding in a patient with multiple hard associated diseases, undergoing an emergency surgery in hemorrhagic shock. The surgery consisted in the resection of the upper polar esogastric, the pathological and immunohistochemistry tests confirming the diagnosis of GIST. The evolution was unfavorable at discharge after 45 days after surgery by an anastomotic fistula.

Central nervous system (CNS) germ cell tumors are very rare, accounting for 0.3-3% of primary intracranial neoplasms; of these, the teratomas are even more uncommon. The immature variant of teratomas, defined by the presence of incompletely differentiated components resembling fetal tissues is considered as having a low, almost borderline malignancy state.

Tuberculosis (TB) is considered a pulmonary disease that can however disseminate to other organs through hematogenous dissemination following primary TB infection. Evolution of the disease can either be precocious, before healing of the primary infection, or late after primary infection, due to reactivation of initial lesions usually because of simultaneous immunosuppressive factors such as diabetes, renal disease, hepatic disease or different type of immunosuppressing treatments. Rare cases when tuberculosis and cancer are diagnosed at the same time create diagnostic difficulties and therapeutic challenges. We present the case of an asymptomatic 52-year-old female that was diagnosed "by chance, at the right moment" with a form of skin melanoma on the right forearm, for which she received a rather well tolerated cytostatic treatment. At the end of this treatment, she was also investigated for a breast mass that proved to be benign; however, enlarged lymph nodes were discovered in the right armpit were discovered upon further investigation. One of the lymph nodes was surgically removed, as first suspicion was of a metastasis from the skin melanoma. However, it was lymph node tuberculosis therefore anti-tuberculosis treatment was initiated. The patient tolerated the treatment with minor side effects. On few occasions, a patient can be diagnosed with incipient stages of skin melanoma and even more rarely the same patient is diagnosed and treated prematurely for lymph node tuberculosis. Sometimes, a successful outcome needs an organized and well-educated patient and a little luck.

Vulvar malignant melanomas are extremely rare neoplasms, representing less than 3% of all cancers in women, 9% of all external genital tract malignancies and 9% of all primary vulvar malignancies. We present the case of a 60-year-old Caucasian patient, who has been admitted in the Clinic of Obstetrics and Gynecology with polymorphic, vulvar local, pelvic-abdominal, genitourinary and general symptoms, being diagnosed with nodular and superficial spreading vulvar melanoma and multiple voluminous uterine leiomyoma with various degenerations. Our study presents the approach of this case in terms of surgical pathology, management, prognosis and outcome. Surgical treatment is the central element of therapeutic management. Vulva melanomas are in general a relatively unpredictable unfavorable prognosis. The sizes of the tumor, the thickness and micro-staging are essential factors for prognosis.

Epithelioid trophoblastic tumor (ETT) is a very rare case of malignant trophoblastic tumor, which can occur particularly during the fertile age of women with a long history of abortion and delivery. ETT originates from the intermediate trophoblastic cells of chorion laeve. The main features of this tumor include lack of vessels within the tumor, nuclear hyperchromasia and pleomorphism and a large zone of necrosis and hyalinization. The clinical features of ETT are specific to each case and often consist of vaginal bleeding or amenorrhea in the absence of other complains. The beta-human chorionic gonadotropin (β-hCG) serum level cannot be an absolute criterion useful in defining diagnosis. The right diagnosis can only be established by a histopathological examination of the tissue picked-up via intrauterine curettage. This paper describes the case of a 35-year-old woman who required gynecological investigation for amenorrhea. The diagnosis established by biopsic curettage and the clinical evolution have influenced the physician's decision to perform hysterectomy. The only method to differentiate between the microscopic diagnosis of ETT and choriocarcinoma was the immunohistochemical staining of trophoblastic cells for cytokeratin AE1÷AE3, p63, Ki67. Despite the diagnosis of malignity, this tumor does not usually require a recommendation for chemotherapy and does not seem to have a bad prognostic. However, these data do not rule out that clinical behavior is sometimes difficult to predict. We analyzed the clinical and histology criteria in line with the data published in literature.

The main target in rectal cancer management is an individualized therapeutic strategy, based on tumor and patient characteristics. The assessment of clinical and pathological factors is important because they represent powerful predictors of the postoperative outcome and have to be considered in the decision making regarding the appropriate surgical technique. The aim of the study was to analyze how the tumor clinical and pathological features correlate with the chosen type of surgical intervention in influencing survival of rectal cancer patients. We ran a retrospective study on 289 patients (N=289) surgically treated for rectal cancer. We analyzed the individual influence of the studied parameter on survival rate in multivariate analysis and we also grouped them in associations of parameter variations and performed a survival analysis for prognostic univariate analysis. For patients with vascular and lymphatic invasion and without perineural invasion, choosing a sphincter function preserving technique brought a better long-term outcome. The TNM stages showed the strongest statistically significant effect upon survival. Patients in T3 or T4 stage benefited best from a performed sphincter saving technique and the positive effect was even higher for those in N1 stage. Assessment of pathological parameters, in association with the type of the surgical procedure, has a strong predictive value upon survival. Sphincter function preserving techniques are followed by good long-term outcome. Accurate preoperative staging can help in choosing the best individualized therapeutic management improving the life expectancy of patients with rectal cancer.

The authors assessed the morphological profile of tumor masses belonging to the small bowel discovered in their daily practice.

E-cadherin and β-catenin are two molecules implicated in cellular adhesion. The reduced expression of β-catenin and E-cadherin is associated with the tumoral epithelial-mesenchymal transition process, a key event in the development of endometrial carcinoma. The aim of our study was to investigate the association between the immunoexpression of β-catenin÷E-cadherin and the tumor differentiation degree, presence of lymph nodes, depth of tumor invasion and pTNM stage of endometrioid endometrial carcinomas in order to enhance the potential aggressiveness of these tumors. Our results revealed significant differences in the expression of β-catenin, when grouping for the tumor stage, invasion in the myometrium and degree of differentiation, as well as significant differences in the expression of E-cadherin for tumor degrees of differentiation. E-cadherin and β-catenin expression was stronger in well-differentiated tumors, superficial myometrium invasion and early tumor stages I or II, thus was associated with better prognostic forms of endometrioid endometrial carcinoma. Our study indicated that decreased of the E-cadherin and β-catenin expression is useful for the assessment of tumor aggressivity.

A tumor represents an abnormal tissue growth that can arise from any ocular structure, such as eyelids, muscles or the optic nerve. At the eyelids, there are two main tumor types: basal cell carcinoma and squamous cell carcinoma. Angiogenesis plays a crucial role in growth, invasion and metastasis processes of any tumor. It is well known the fact that without new vessels formation tumors cannot exceed 1-2 mm diameter. Immunohistochemical analysis has been performed on 43 cases of primary carcinomas of the eyelid, diagnosed between 2010 and 2014 in the Laboratory of Pathological Anatomy of the University Emergency County Hospital of Craiova, Romania. Biological material was represented by surgical resection samples, coming from the Clinic of Ophthalmology the anteriorly named Hospital. Within the immunohistochemical study, we have evaluated epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) expression in a group of 43 cutaneous carcinomas of the eyelid, depending on the type and differentiation grade of the tumor. Of the 43 samples, 23 came from patients with eyelid basal cell carcinoma and 20 came from patients with eyelid squamous cell carcinoma. In our study, EGFR and VEGF immunoexpression was superior for squamous cell carcinomas, compared to basal cell carcinomas, fact that was statistically significant. Regarding squamous cell carcinomas, the immunoexpression of these two markers was superior in moderate÷poor differentiated forms, compared to well differentiated forms, fact that was statistically significant. The markers used in this study were found to be associated with the acquisition of aggression and angiogenic phenotypes by analyzed carcinomas.

The clinical significance of the Epstein-Barr virus (EBV) status and p16 expression was unknown in nasopharyngeal carcinoma (NPC).

A causal link between overexpression of aryl hydrocarbon receptor (AHR) and its target cytochrome P450 1A1 (CYP1A1) and metastatic outgrowth of various cancer entities has been established. Nevertheless, the mechanism how AHR/CYP1A1 support metastasis formation is still little understood. In vitro we discovered a potential mechanism facilitating tumour dissemination based on the production of 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE). Utilising a three-dimensional lymph endothelial cell (LEC) monolayer & MDA-MB231 breast cancer cell spheroid co-culture model in combination with knock-down approach allowed elucidation of the molecular/biochemical basis of AHR/CYP1A1-induced tumour breaching through the LEC barrier. Enzyme immunoassay evidenced the potential of recombinant CYP1A1 to synthesise 12(S)-HETE in vitro and qPCR and Western blotting measured gene and protein expression in specific experimental settings. In detail, AHR induced CYP1A1 expression and 12(S)-HETE secretion in tumour spheroids, which caused LEC junction retraction thereby forming large discontinuities allowing transmigration of the tumour. This was enforced by the activating AHR ligand 6-formylindolo (3,3-b)carbazole (FICZ), or inhibited by the AHR antagonist 3,3’-diindolylmethane (DIM) as well as by siRNA against AHR and CYP1A1. AHR and NF-κB were negatively cross talking and therefore, the inhibition of AHR (but not CYP1A1) induced RELA, RELB, NFKB1, NFKB2 and the NF-κB target MMP1, which itself promotes tumour intravasation by a mechanism that is different from 12(S)-HETE. Conversely, the inhibition of NFKB2 induced AHR, CYP1A1 and 12(S)-HETE synthesis. The approved clinical drugs guanfacine and vinpocetine, which inhibit CYP1A1 and NF-κB, respectively, significantly inhibited LEC barrier breaching in vitro indicating an option to reduce metastatic dissemination.

Adipose-derived stem cells (ADSCs) have led to growing interest in cell-based therapy because they can be easily harvested from an abundant tissue. ADSCs must be expanded in vitro before transplantation. This essential step causes concerns about the safety of adult stem cells in terms of potential transformation. Tumorigenesis is driven in its earliest step by DNA replication stress, which is characterized by the accumulation of stalled DNA replication forks and activation of the DNA damage response. Thus, to evaluate the safety of ADSCs during ex vivo expansion, we monitored DNA replication under atmospheric (21%) or physiologic (1%) oxygen concentration. Here, by combining immunofluorescence and DNA combing, we show that ADSCs cultured under 21% oxygen accumulate endogenous oxidative DNA lesions, which interfere with DNA replication by increasing fork stalling events, thereby leading to incomplete DNA replication and fork collapse. Moreover, we found by RNA sequencing (RNA-seq) that culture of ADSCs under atmospheric oxygen concentration leads to misexpression of cell cycle and DNA replication genes, which could contribute to DNA replication stress. Finally, analysis of acquired small nucleotide polymorphism shows that expansion of ADSCs under 21% oxygen induces a mutational bias toward deleterious transversions. Overall, our results suggest that expanding ADSCs at a low oxygen concentration could reduce the risk for DNA replication stress-associated transformation, as occurs in neoplastic tissues. Stem Cells Translational Medicine 2017;6:68-76.

Adult mesenchymal stromal cell-based interventions have shown promising results in a broad range of diseases. However, their use has faced limited effectiveness owing to the low survival rates and susceptibility to environmental stress on transplantation. We describe the cellular and molecular characteristics of multilineage-differentiating stress-enduring (Muse) cells derived from adipose tissue (AT), a subpopulation of pluripotent stem cells isolated from human lipoaspirates. Muse-AT cells were efficiently obtained using a simple, fast, and affordable procedure, avoiding cell sorting and genetic manipulation methods. Muse-AT cells isolated under severe cellular stress, expressed pluripotency stem cell markers and spontaneously differentiated into the three germ lineages. Muse-AT cells grown as spheroids have a limited proliferation rate, a diameter of ∼15 µm, and ultrastructural organization similar to that of embryonic stem cells. Muse-AT cells evidenced high stage-specific embryonic antigen-3 (SSEA-3) expression (∼60% of cells) after 7-10 days growing in suspension and did not form teratomas when injected into immunodeficient mice. SSEA-3+ -Muse-AT cells expressed CD105, CD29, CD73, human leukocyte antigen (HLA) class I, CD44, and CD90 and low levels of HLA class II, CD45, and CD34. Using lipopolysaccharide-stimulated macrophages and antigen-challenged T-cell assays, we have shown that Muse-AT cells have anti-inflammatory activities downregulating the secretion of proinflammatory cytokines, such as interferon-γ and tumor necrosis factor-α. Muse-AT cells spontaneously gained transforming growth factor-β1 expression that, in a phosphorylated SMAD2-dependent manner, might prove pivotal in their observed immunoregulatory activity through decreased expression of T-box transcription factor in T cells. Collectively, the present study has demonstrated the feasibility and efficiency of obtaining Muse-AT cells that can potentially be harnessed as immunoregulators to treat immune-related disorders. Stem Cells Translational Medicine 2017;6:161-173.

Introduction/Background : evolution of the cancerous disease sometimes results in externalization of the tumor to the skin, creating a malignant wound. Limited data describe the coping strategies that individuals will use to deal with this situation. Aim : the main objective is to determine the different strategies of adaptations used by patients with malignant wounds, and links with their clinical and sociodemographic characteristics. Secondary objective is to document body image of these individuals. Materials and methods : an analytic study was proposed to 21 patients with a malignant wound, hospitalized in medical oncology. The French versions of the scale of coping Vitaliano and scale of body image (Body Image Scale) were used. Results : patients with malignant wound use three coping strategies : problem, emotional and social support research : the pain at the wound is positively associated with emotional coping and seniority of the cancer diagnosis to seeking social support. Body image seems impaired. Discussion/Conclusion : adjusting to the malignant wound seems possible with the support care provision such as pain relief and/or counseling. A national study is currently trying to generalize these results.

Lactoferrin (Lf) is an iron-binding glycoprotein that is present at high concentrations in milk. Bovine lactoferricin (LfcinB) is a peptide fragment generated by pepsin proteolysis of bovine lactoferrin (bLf). LfcinB consists of amino acid residues 17-41 proximal to the N-terminus of bLf and a disulfide bond between residues 19 and 36, forming a loop. Both bLf and LfcinB have been demonstrated to have antitumor activities. Colorectal cancer is the second most common cause of cancer death in developed countries. We hypothesized that bLf and LfcinB exert antitumor activities on colon cancer cells (HT-29) by triggering various signaling pathways. bLf and LfcinB significantly induced apoptosis in HT-29 cells but not in normal human intestinal epithelial cells, as revealed by the ApoTox-Glo Triplex Assay. The LIVE/DEAD cell viability assay showed that both bLf and LfcinB reduced the viability of HT-29 cells. Transcriptome analysis indicated that bLf, cyclic LfcinB, and linear LfcinB exerted antitumor activities by differentially activating diverse signaling pathways, including p53, apoptosis, and angiopoietin signaling. Immunoblotting results confirmed that both bLf and LfcinBs increased expression of caspase-8, p53, and p21, critical proteins in tumor suppression. These results provide valuable information regarding bLf and LfcinB for potential clinical applications in colon cancer therapy.

Colorectal cancer (CRC) is the fourth most prevalent cancer globally. Several factors have roles in cancer establishment. One of the most important factors is hypoxia that induces hypoxia inducible factor-1 (HIF-1). The HIF-1 alpha overexpressed in hypoxia conditions and plays a pivotal role in carcinogenesis features. In this study, we aimed to examine the efficiency of HIF-1 alpha gene expression at mRNA and protein's level for CRC diagnosing and staging.